Weaning in mammals is associated with a shift in the metabolism, driven by the differences in the macronutrient composition of milk and post-weaning diet. Milk has a higher fat content compared with the carbohydrate-enriched solid food. Malnutrition during this stage could affect this transition with long-term adverse effects. The role of micronutrients during this transition is not well understood.

We used mice lacking a functional vitamin D receptor (VDR) to study the role of vitamin D signalling in the metabolic transition during weaning.

We demonstrate that after weaning, VDR knockout mice exhibit systemic energy deprivation and higher lipolysis in inguinal white adipose tissue, probably due to increased norepinephrine signalling via protein kinase A (PKA) and extracellular signalling-regulated kinase (ERK) pathways. The energy deprivation in vdr-/- mice is associated with defective liver glycogenolysis, characterized by increased expression of protein phosphatase-1 alpha and decreased glycogen phosphorylase activity. However, restoration of serum calcium and phosphate levels by a rescue diet is sufficient to restore energy metabolism in vdr-/- mice. Interestingly, maintaining a high-fat-containing milk-based diet post-weaning could prevent the onset of energy deprivation, liver glycogen storage defect, and adipose atrophy in these mice.

Our data show that vitamin D-signalling is essential for the adaptation of mice to the dietary shift from high-fat-containing milk to post-weaning carbohydrate-enriched diets. It also reveals a novel macronutrient-micronutrient interaction that shapes the metabolic flexibility of the individual based on the dietary composition of nutrients.

The current study aimed to evaluate the role of cerium oxide nanoparticles (C-1), a potent antioxidant, in the medication of cardiovascular disease in obese animal model. C-1 was prepared using a modified sonication sol-gel method. Thirty-two adult male rats were equally divided into 4 groups (n=8/each). The first (control) and second (obese) groups are not treated while the obese rats in the third and fourth groups were given 15 and 30 mg/kg C-1(IP), respectively, for 8 weeks. Parameters of insulin resistance, adipocyte hormones, inflammatory markers, lipid profile, cardiac enzymes and cardiac iron content (C-Fe) were estimated. Moreover, histological study and immunohistochemical stain for inducible nitric oxide synthase (INOS) for cardiac and aortic tissues were performed. The XRD patterns of C-1 showed narrow symmetric diffraction peaks. The particle diameters were calculated from the TEM histogram (21.09 nm) and the Debye-Scherrer Method (20.74 nm) which were very similar. Using the most intense peak ( 28 . 47 ∘ ), structural parameters were calculated including nano-crystallite size, Micro-strain, Lorentz factor, Thomson polarization parameter, and Lorentz polarization parameter. BET was used to calculate The total surface area (ST ), and specific surface area (SBET ). The XPS survey spectrum of C-1 showed peaks for C-1s, O-1s and Ce-3d. The treatment of obese rats with C-1 led to a significant decrease in body weight, C-Fe , plasma leptin, tumor necrosis factor-alpha (TNF α ), interleukin-6 (IL6), C-reactive protein (CRP), resistin, cholesterol, triglycerides, low-density lipoprotein (LDL), Troponin, Creatinine Kinase-MB (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA) in cardiac tissue or in plasma. Also, C-1 lowered plasma monocyte chemoattractant protein-1 (MCP-1), Epithelial Neutrophil-Activating Peptide (ENA-78), and insulin and glucose levels in obese rats. Furthermore, C-1 alleviated the increase of cardiac iNOS. Moreover, C-1 mitigated pathological changes of cardiac muscle and aorta observed in obese rats. On the other hand, C-1 enhanced adiponectin, cardiac glutathione (GSH) and superoxide dismutase (SOD) in obese rats. The effect of C-1 is dose-dependent ( 30 mg/kg of C-1 is more evident than 15 mg/kg). The modified synthesis method may lead to a smaller particle size than that reported in our previously reported work. The XRD patterns of C-1 indicate its cubic structure with space group F m -3 m (225) which was matched by code id 4343161 from COD. The Raman spectrum of C-1 indicates the absence of rearrangement oxygen atoms, the presence of oxygen in its fluorite lattice positions, and the oxygen vacancies in C-1 and the Ce vibration model (F2g). The presence of ten peaks in the high-resolution Ce-3d XP spectrum indicates the existence of both Ce3+ and Ce4+. C-1 showed therapeutic efficacy in atherosclerosis and cardiac muscle abnormalities associated with obese rats, probably because of their antioxidant and anti-inflammatory properties, which lead to lowering oxidative stress.

Adiponectin is an abundantly secreted hormone that communicates information between the adipose tissue, and the immune and cardiovascular systems. In metabolically healthy individuals, adiponectin is usually found at high levels and helps improve insulin responsiveness of peripheral tissues, glucose tolerance, and fatty acid oxidation. Beyond its metabolic functions in insulin-sensitive tissues, adiponectin plays a prominent role in attenuating the development of atherosclerotic plaques, partially through regulating macrophage-mediated responses. In this context, adiponectin binds to its receptors, adiponectin receptor 1 (AdipoR1) and AdipoR2 on the cell surface of macrophages to activate a downstream signaling cascade and induce specific atheroprotective functions. Notably, macrophages modulate the stability of the plaque through their ability to switch between proinflammatory responders, and anti-inflammatory proresolving mediators. Traditionally, the extremes of the macrophage polarization spectrum span from M1 proinflammatory and M2 anti-inflammatory phenotypes. Previous evidence has demonstrated that the adiponectin-AdipoR pathway influences M1-M2 macrophage polarization; adiponectin promotes a shift toward an M2-like state, whereas AdipoR1- and AdipoR2-specific contributions are more nuanced. To explore these concepts in depth, we discuss in this review the effect of adiponectin and AdipoR1/R2 on 1) metabolic and immune responses, and 2) M1-M2 macrophage polarization, including their ability to attenuate atherosclerotic plaque inflammation, and their potential as therapeutic targets for clinical applications.

Geese are susceptible to oxidative stress during breeding, leading to senescence of granulosa cells (GCs) and reduced egg production. Adiponectin (ADPN) is a cytokine secreted by adipose tissue that functions to regulate metabolism and antioxidants. However, its role in the regulation of goose GCs is unclear. To investigate this, senescence in primary goose GCs was induced by D-gal and assessed via RT‒qPCR, senescence-associated β-galactosidase (SA-β-gal) staining, immunofluorescence, flow cytometry, and transcriptomics. The effect of ADPN on GC senescence was investigated by overexpressing and knocking down ADPN expression. The results showed that ADPN could alleviate oxidative stress and cell cycle arrest in GCs, reduce the expression of the senescence-associated secretory phenotype (SASP)-related genes IL-6 and IL-8, regulate the metabolic capacity of GCs, reduce the accumulation of SA-β-gal, maintain telomere length, and alleviate the senescence of GCs induced by D-gal. The RNA-seq results provided further evidence for the regulatory effect of ADPN on GC senescence. ADPN was shown to attenuate oxidative stress-induced GC senescence through the AGE (Advanced glycation end products)-RAGE (Receptor of advanced glycation end products) and NOD-like receptor pathways. These findings may contribute to the development of improved theoretical references for improving egg-laying performance and prolonging the service life of geese.

The research aimed to examine the impact of coated cysteamine (CS) and choline chloride (CC) on relieving the pathological effects of fatty liver hemorrhagic syndrome (FLHS) in laying hens. FLHS was induced by a high-energy low-protein (HELP) diet. Ninety laying hens were equally divided into 5 treatments with 6 replicates per treatment (3 hens/replicate). The control treatment (Cont) was fed a basal diet, while the remaining treatments were fed a HELP diet. Under the HELP dietary plan, 4 treatments were set by a 2 × 2 factorial design. Two levels of CS (CS-: 0.00 mg/kg CS; CS+: 100 mg/kg diet) and 2 levels of choline (CC-: 1,182 mg/kg; CC+: 4,124 mg/kg) were set and named CS-CC- (HELP), CS+CC-, CS-CC+ and CS+CC+. The liver of the CS-CC- (HELP) group became yellowish-brown and greasy, with hemorrhages and bleeding spots. Elevated (P < 0.05) plasma and hepatic ALT and AST and hepatic MDA levels, combined with reduced (P < 0.05) plasma and hepatic SOD and GSH-Px activities in the CS-CC- (HELP) group proved that FLHS was successfully induced. Dietary supplementation of CS, CC, or both (CS+CC+) in HELP diets relieved the pathological changes, significantly (P < 0.05) reduced the AST and ALT levels, and strengthened the antioxidant potential in laying hens under FLHS. The highest (P < 0.001) plasma adiponectin concentration was observed in the CS+CC- and lowest in the CS-CC- (HELP) group. In addition, CS and CC supplementation lowers the elevated levels of hepatic T-CHO and TG by increasing the HDL-C and reducing LDL-C levels (P < 0.05) than CS-CC- (HELP) group. CS supplementation, either alone or with CC, helps laying hens restore their egg production. It could be stated that CS and CC supplements could ameliorate the adverse effects of FLHS by regulating antioxidant enzymes activities, modulating the hepatic lipid metabolism, and restoring the production performance in laying hens. Hence, adding CS and CC could be an effective way to reduce FLHS in laying hens.

Alzheimer's disease (AD) is a degenerative brain disease that affects millions of people worldwide. It is caused by abnormalities in cholinergic neurons, oxidative stress, and inflammatory cascades. The illness is accompanied by personality changes, memory issues, and dementia. Metabolic signaling pathways help with fundamental processes like DNA replication and RNA transcription. Being adaptable is essential for both surviving and treating illness. The body's metabolic signaling depends on adipokines, including adiponectin (APN) and other adipokines secreted by adipose tissues. Energy homeostasis is balanced by adipokines, and nutrients. Overconsumption of nutrients messes with irregular signaling of adipokines, such as APN in both peripheral and brain which leads to neurodegeneration, such as AD. Despite the failure of traditional treatments like memantine and cholinesterase inhibitors, natural plant bioactive substances like Osmotin (OSM) have been given a focus as potential therapeutics due to their antioxidant properties, better blood brain barrier (BBB) permeability, excellent cell viability, and especially nanoparticle approaches. The review highlights the published preclinical literature regarding the role of OSM in AD pathology while there is a need for more research to investigate the hidden therapeutic potential of OSM which may open a new gateway and further strengthen its healing role in the pathogenesis of neurodegeneration, especially AD.

Body mass index (BMI) is inversely proportional with adiponectin levels among adults, while insulin, C-reactive protein (CRP), interleukin 6 (IL-6), resistin and tumor necrosis factor-alpha (TNF-α) have been linked with elevated BMI. The role and relation of these biomarkers with BMI among a Hispanic pediatric population are less known. Thus, the objective of this study was to examine the association of inflammatory markers with the odds of overweight/obesity while controlling for several sociodemographic factors among a Hispanic youth population in Northeast Tennessee.

Height, weight, demographic information, and blood samples were collected from 107 Hispanic children aged 2 to 10 years recruited at a large community health center in 2015-2016 in Northeast Tennessee. Data for this research were accessed and analyzed in 2022. Multivariable logistic regression was conducted to assess the relations between adiponectin, insulin, resistin, CRP, TNF-α, and IL-6, and overweight/obesity vs. having a healthy (normal) weight.

Adiponectin levels were significantly lower among overweight/obese Hispanic children (p = 0.0144) compared to healthy weight children. The odds of overweight/obesity decreased by 4% for every one-unit increase in serum adiponectin. Insulin levels were significantly higher among overweight/obese Hispanic children compared to healthy weight children (p = 0.0048). The odds of overweight/obesity increased by 7% for every one-unit increase in serum insulin. Resistin, IL-6, TNF-α, and CRP were not significantly associated with overweight/obesity in this population.

Adiponectin behaves similarly in Hispanic youth as it does in other pediatric populations, possibly making it a valuable marker when examining metabolic health status in this population.

Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles. Given the many unwanted side effects that accompany current anti-inflammatory steroid-based approaches for treating DMD (e.g., glucocorticoids), there is a need to develop new therapies that address inflammation and other cellular dysfunctions. Adiponectin receptor (AdipoR) agonists, which stimulate AdipoR1 and R2 isoforms on various cell types, have emerged as therapeutic candidates for DMD due to their anti-inflammatory, anti-fibrotic, and pro-myogenic properties in pre-clinical human and rodent DMD models. Although these molecules represent a new direction for therapeutic intervention, the mechanisms through which they elicit their beneficial effects are not yet fully understood, and DMD-specific data is limited. The overarching goal of this review is to investigate how adiponectin signaling may ameliorate pathology associated with dystrophin deficiency through inflammatory-dependent and -independent mechanisms and to determine if current data supports their future progression to clinical trials.

Geese are susceptible to oxidative stress during reproduction, which can lead to follicular atresia and impact egg production. Follicular atresia is directly triggered by the apoptosis and autophagy of granulosa cells (GCs). Adiponectin (ADPN), which is secreted by adipose tissue, has good antioxidant and anti-apoptotic capacity, but its role in regulating the apoptosis of GCs in geese is unclear. To investigate this, this study examined the levels of oxidative stress, apoptosis, and autophagy in follicular tissues and GCs using RT-qPCR, Western blotting, immunofluorescence, flow cytometry, transcriptomics and other methods. Atretic follicles exhibited high levels of oxidative stress and apoptosis, and autophagic flux was obstructed. Stimulating GCs with H2O2 produced results similar to those of atretic follicles. The effects of ADPN overexpression and knockdown on oxidative stress, apoptosis and autophagy in GCs were investigated. ADPN was found to modulate autophagy and reduced oxidative stress and apoptosis in GCs, in addition to protecting them from H2O2-induced damage. These results may provide a reasonable reference for improving egg-laying performance of geese.

The diverse beneficial effects of adiponectin-receptor signaling, including its impact on the regulation of inflammatory processes in vivo, have resulted in development of adiponectin receptor agonists as a treatment for metabolic disorders. However, there are no established non-invasive bioassays for detection of adiponectin target engagement in humans or animal models. Here, we designed an assay using small amounts of blood to assess adiponectin action. Specifically, we tested effects of the small 10-amino acid peptide adiponectin receptor agonist, ALY688, in a sublethal LPS endotoxemia model in mice. LPS-induced pro-inflammatory cytokine levels in serum were significantly reduced in mice treated with ALY688, assessed via multiplex ELISA in flow cytometry. Furthermore, ALY688 alone significantly induced TGF-β release in serum 1 h after treatment and was elevated for up to 24 h. Additionally, using a flow-cytometry panel for detection of changes in circulating immune cell phenotypes, we observed a significant increase in absolute T cell counts in mice after ALY688 treatment. To assess changes in intracellular signaling effectors downstream of adiponectin, phospho-flow cytometry was conducted. There was a significant increase in phosphorylation of AMPK and p38-MAPK in mice after ALY688 treatment. We then used human donor immune cells (PBMCs) treated with ALY688 ex vivo and observed elevation of AMPK and p38-MAPK phosphorylation from baseline in response to ALY688. Together, these results indicate we can detect adiponectin action on immune cells in vivo by assessing adiponectin signaling pathway for AMPK and p38-MAPK, as well as pro-inflammatory cytokine levels. This new approach provides a blood-based bioassay for screening adiponectin action.

Obesity and related metabolic syndromes have been recognized as important disease risks, in which the role of adipokines cannot be ignored. Adiponectin (ADP) is one of the key adipokines with various beneficial effects, including improving glucose and lipid metabolism, enhancing insulin sensitivity, reducing oxidative stress and inflammation, promoting ceramides degradation, and stimulating adipose tissue vascularity. Based on those, it can serve as a positive regulator in many metabolic syndromes, such as type 2 diabetes (T2D), cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), sarcopenia, neurodegenerative diseases, and certain cancers. Therefore, a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors. The modulation of ADP genes, multimerization, and secretion covers the main processes of ADP generation, providing a comprehensive orientation for the development of more appropriate therapeutic strategies. In order to have a deeper understanding of ADP, this paper will provide an all-encompassing review of ADP.

Obesity is among the risk factors for male infertility. Although several mechanisms underlying obesity-induced male subfertility have been reported, the entire mechanism of obesity-induced male infertility still remains unclear. Here, we show that sperm count, sperm motility and sperm fertilizing ability were decreased in male mice fed a high-fat diet and that the expression of the AdipoR1 gene and protein was decreased, and the expression of pro-apoptotic genes and protein increased, in the testis from mice fed a high-fat diet. Moreover, we demonstrate that testes weight, sperm count, sperm motility and sperm fertilizing ability were significantly decreased in AdipoR1 knockout mice compared to those in wild-type mice; furthermore, the phosphorylation of AMPK was decreased, and the expression of pro-apoptotic genes and proteins, caspase-6 activity and pathologically apoptotic seminiferous tubules were increased, in the testis from AdipoR1 knockout mice. Furthermore, study findings show that orally administrated AdipoRon decreased caspase-6 activity and apoptotic seminiferous tubules in the testis, thus ameliorating sperm motility in male mice fed a high-fat diet. This was the first study to demonstrate that decreased AdipoR1/AMPK signaling led to increased caspase-6 activity/increased apoptosis in the testis thus likely accounting for male infertility.

Myocardial ischemia-reperfusion injury (MIRI) is widespread in the treatment of ischemic heart disease, and its treatment options are currently limited. Adiponectin (APN) is an adipocytokine with cardioprotective properties; however, the mechanisms of APN in MIRI are unclear. Therefore, based on preclinical (animal model) evidence, the cardioprotective effects of APN and the underlying mechanisms were explored.

The literature was searched for the protective effect of APN on MIRI in six databases until 16 November 2023, and data were extracted according to selection criteria. The outcomes were the size of the myocardial necrosis area and hemodynamics. Markers of oxidation, apoptosis, and inflammation were secondary outcome indicators. The quality evaluation was performed using the animal study evaluation scale recommended by the Systematic Review Center for Laboratory animal Experimentation statement. Stata/MP 14.0 software was used for the summary analysis.

In total, 20 papers with 426 animals were included in this study. The pooled analysis revealed that APN significantly reduced myocardial infarct size [weighted mean difference (WMD) = 16.67 (95% confidence interval (CI) = 13.18 to 20.16, P < 0.001)] and improved hemodynamics compared to the MIRI group [Left ventricular end-diastolic pressure: WMD = 5.96 (95% CI = 4.23 to 7.70, P < 0.001); + dP/dtmax: WMD = 1393.59 (95% CI = 972.57 to 1814.60, P < 0.001); -dP/dtmax: WMD = 850.06 (95% CI = 541.22 to 1158.90, P < 0.001); Left ventricular ejection fraction: WMD = 9.96 (95% CI = 7.29 to 12.63, P < 0.001)]. Apoptosis indicators [caspase-3: standardized mean difference (SMD) = 3.86 (95% CI = 2.97 to 4.76, P < 0.001); TUNEL-positive cells: WMD = 13.10 (95% CI = 8.15 to 18.05, P < 0.001)], inflammatory factor levels [TNF-α: SMD = 4.23 (95% CI = 2.48 to 5.98, P < 0.001)], oxidative stress indicators [Superoxide production: SMD = 4.53 (95% CI = 2.39 to 6.67, P < 0.001)], and lactate dehydrogenase levels [SMD = 2.82 (95% CI = 1.60 to 4.04, P < 0.001)] were significantly reduced. However, the superoxide dismutase content was significantly increased [SMD = 1.91 (95% CI = 1.17 to 2.65, P < 0.001)].

APN protects against MIRI via anti-inflammatory, antiapoptotic, and antioxidant effects, and this effect is achieved by activating different signaling pathways.

The pituitary gland is a key endocrine gland in all classes of vertebrates, including mammals. The pituitary gland is an important component of hypothalamus-pituitary-target organ hormonal regulatory axes and forms a functional link between the nervous system and the endocrine system. In response to hypothalamic stimuli, the pituitary gland secretes a number of hormones involved in the regulation of metabolism, stress reactions and environmental adaptation, growth and development, as well as reproductive processes and lactation. In turn, hormones secreted by target organs at the lowest levels of the hormonal regulatory axes regulate the functions of the pituitary gland in the process of hormonal feedback. The pituitary also responds to other peripheral signals, including adipose-tissue-derived factors. These substances are a broad group of peptides known as adipocytokines or adipokines that act as endocrine hormones mainly involved in energy homeostasis. Adipokines, including adiponectin, resistin, apelin, chemerin, visfatin, and irisin, are also expressed in the pituitary gland, and they influence the secretory functions of this gland. This review is an overview of the existing knowledge of the relationship between chosen adipose-derived factors and endocrine functions of the pituitary gland, with an emphasis on the pituitary control of reproductive processes.

Epidemiological data and research highlight increased neuropathy and chronic pain prevalence among females, spanning metabolic and normometabolic contexts, including murine models. Prior findings demonstrated diverse immune and neuroimmune responses between genders in neuropathic pain (NeP), alongside distinct protein expression in sciatic nerves. This study unveils adipose tissue's (AT) role in sex-specific NeP responses after peripheral nerve injury. Metabolic assessments, metabolomics, energy expenditure evaluations, AT proteomic analyses, and adipokine mobilization depict distinct AT reactions to nerve damage. Females exhibit altered lipolysis, fatty acid oxidation, heightened energy expenditure, and augmented steroids secretion affecting glucose and insulin metabolism. Conversely, male neuropathy prompts glycolysis, reduced energy expenditure, and lowered unsaturated fatty acid levels. Males' AT promotes regenerative molecules, oxidative stress defense, and stimulates peroxisome proliferator-activated receptors (PPAR-γ) and adiponectin. This study underscores AT's pivotal role in regulating gender-specific inflammatory and metabolic responses to nerve injuries, shedding light on female NeP susceptibility determinants.

There is a high frequency of overweight and obesity in women of reproductive age. Women who start pregnancy with overweight or obesity have an increased risk of developing maternal obstetric complications such as gestational hypertension, pre-eclampsia, gestational diabetes mellitus, postpartum hemorrhage, and requiring C-section to resolve the pregnancy with a higher risk of C-section surgical site infection. Excessive weight in pregnancy is characterized by dysregulation of adipokines, the functions of which partly explain the predisposition of pregnant women with overweight or obesity to these maternal obstetric complications. This review compiles, organizes, and analyzes the most recent studies on adipokines in pregnant women with excess weight and the potential pathophysiological mechanisms favoring the development of maternal pregnancy complications.

Obesity is a complicated disease characterized by abundant fat accumulation. It is associated with cardiovascular disease. The current study aimed to appreciate the role of synthesized zinc oxide nanoparticles (ZnONPs) (18.72 nm in size) in curbing cardiovascular disease in an obesity model of a high fat/sucrose diet in male rats. For 16 weeks, 24 rats were fed a high-fat diet and a 25% sucrose solution to develop obesity, and after that, the rats were randomly allocated into four groups of rats. Group 1 served as the control group and consisted of normal, non-obese rats. Group 2 comprised obese rats that were injected with an equivalent volume of a neutral substance, serving as vehicle control. In Group 3 or 4, obese rats were treated with an intraperitoneal injection of 5 or 10mg/kg of zinc oxide nanoparticles (ZnONPs) for eight weeks. The treatment of obese rats with ZnONPs decreased plasma levels of monocyte chemoattractant Protein-1 (MCP-1), resistin, ENA78, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), and C reactive protein (CRP). Also, the remediation of obese rats with ZnONPs led to a significant decrease in body mass index (BMI), body weight gain, leptin, cholesterol, triglycerides, LDL (Low-density lipoprotein), glucose, and insulin resistance index (HOMA-IR). Moreover, ZnONPs treatment lowered troponin, creatine phosphokinase-MB (CK-MB), lactate dehydrogenase (LDH), cardiac or adipose tissue iron content, and malondialdehyde (MDA) either in blood or heart tissue. Otherwise, treating obese rats with ZnONPs enhanced plasma adiponectin levels, cardiac-reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, ZnONPs displayed a significant influence on the cardiovascular system since they combat the rise in blood pressure and the pathological changes of the heart and aorta besides maintaining plasma nitric oxide levels. The results showed a positive correlation between BMI and MDA, MPC-1, CK-MB, and LDH. ZnONPs are convenient in treating cardiovascular disease in obese rats via reduced blood pressure, oxidative stress, cardiac iron accumulation, insulin resistance, and inflammatory markers.

This cross-sectional study explores the association of adipokines and interleukin-6 (IL-6) with muscle and protein energy wasting (PEW) in children with chronic kidney disease (CKD).

We measured serum adiponectin, leptin, resistin and IL-6 in 53 patients with CKD stage 3-5. Lean tissue (LTI) and fat tissue index (FTI) were estimated by bioimpedance analysis spectroscopy. PEW was defined as muscle wasting [LTI adjusted to height age (LTI HA) z-score < -1.65 SD) and at least 2 of the following: reduced body mass [body mass index adjusted to height age (BMI HA) z-score < -1.65 SD), poor growth [height z-score < -1.88 SD], questionnaire-based decreased appetite, and serum albumin ≤3.8 g/dL.

PEW, observed in 8 (15.1%) patients, was more prevalent in CKD stage 5 (P = .010). Among the adipokines, adiponectin, and resistin levels were significantly higher in CKD stage 5 (P < .001, P = .005). Adiponectin was correlated to LTI HA z-score (Rs = -0.417, P = .002), leptin to FTI z-score (Rs = 0.620, P < .001), while no correlation was observed between resistin and body composition parameters. Resistin was the only adipokine correlated to IL-6 (Rs = 0.513, P < .001). After adjustment for CKD stage and patient age, PEW was associated with adiponectin and IL-6 rise by 1 μg/mL and 10 pg/mL respectively (odds ratio (OR) 1.240, 95% confidence interval (CI) 1.040, 1.478 and OR 1.405, 95% CI 1.075-1.836) but not with leptin, while resistin association with PEW lost its significance.

In pediatric CKD, adiponectin is associated with muscle wasting, leptin with adiposity and resistin with systemic inflammation. Adiponectin and cytokine IL-6 may serve as PEW biomarkers.

Adipose tissue, being an organ of the endocrine system, can influence the severity of chronic obstructive pulmonary disease (COPD). Even though several inflammatory markers can potentially significantly influence lung function, the precise function of adipokines, like adiponectin, in COPD is still disputed. To analyze the association of COPD with adiponectin concentrations, a meta-analysis of the most recent literature and single-cell sequencing data were conducted.

Studies in Embase, PubMed, Cochrane Library, and Web of Science were browsed to obtain relevant data, which were then assessed with the aid of R 4.1.3 and STATA 11.0 software. Standardized mean differences and correlation coefficients aided the analysis of effect values. Moreover, a single-cell sequencing GSE136831 dataset was retrieved to ascertain the mRNA expression of adiponectin gene (ADIPOQ) in the lung tissue of COPD patients to confirm the difference in the expression of adiponectin between the case and control groups.

This meta-analysis comprised 18 publications involving 24 studies. The overall combined data established the concentration of plasma/serum adiponectin as significantly higher in patients with COPD compared to healthy subjects. Subgroup analyses based on disease status, specimen type, ethnicity, study design method, measurement method, and age of COPD patients demonstrated that all patients with COPD had elevated levels of adiponectin compared to healthy controls. When subgroup analysis was performed for gender alone, the results depicted that male COPD patients had significantly higher adiponectin than healthy males, while female patients of COPD had elevated adiponectin compared to healthy females. Furthermore, it was found that plasma/serum adiponectin appeared to be positively correlated with tumor necrosis factor-α, and it was negatively correlated with FEV1% and FEV1/FVC. The results of single-cell sequencing data suggested that ADIPOQ mRNA was mainly expressed in alveolar epithelial cells, and the level of ADIPOQ mRNA was higher in lung tissues of patients with COPD than in lung tissues of healthy subjects.

This meta-analysis suggests that the levels of plasma/serum adiponectin are significantly elevated in patients with COPD versus controls. Tumor necrosis factor-α, FEV1/FVC, and FEV1% may all be associated with the concentrations of adiponectin.

Obesity, impaired glycemic control, and hepatic steatosis often coexist and are risk factors for developing dementia, and Alzheimer's disease (AD). We hypothesized that a therapeutic agent that improves glycemic control and steatosis may attenuate obesity-associated progression of dementia. We previously identified that adenoviral protein E4orf1 improves glycemic control and reduces hepatic steatosis despite obesity in mice. Here, we determined if this metabolic improvement by E4orf1 will ameliorate cognitive decline in a transgenic mouse model of AD.

Fourteen- to twenty-month-old APP/PS1/E4orf1 and APP/PS1 (control) mice were fed a high-fat diet. Cognition was determined by Morris Water Maze (MWM). Systemic glycemic control and metabolic signaling changes in adipose tissue, liver, and brain were determined.

Compared to control, E4orf1 expression significantly improved glucose clearance, reduced endogenous insulin requirement and lowered body-fat, enhanced glucose and lipid metabolism in adipose tissue, and reduced de novo lipogenesis in the liver. In the brain, E4orf1 mice displayed significantly greater expression of genes involved in neurogenesis and amyloid-beta degradation and performed better in MWM testing.

This study opens-up the possibility of addressing glycemic control and steatosis for attenuating obesity-related cognitive decline. It also underscores the potential of E4orf1 for the purpose, which needs further investigations.

The increasing prevalence of obesity has prompted intensive research into understanding its role in pathogenesis and designing appropriate treatments. To determine the signals generated from the interaction of fat cells with a target organ, a reliable white adipocyte model in vitro is needed. Differentiated fibroblasts are the most extensively studied using in vitro cell models of white adipocytes. However, it can be argued that differentiated fibroblasts minimally recapitulate the consequences of obesity. Here, we describe 3T3-L1 MBX cells as a culture model for studying obese adipocytes and their effects. Differentiation of 3T3-L1 MBX cells was at first optimized and then maintained in the presence of fatty acids cocktail combination to induce the obese condition. Lipid accumulation and adipokine secretion profiles were analyzed. Results showed that fatty acid-maintained, differentiated 3T3-L1 MBX cells had significantly greater accumulation of lipids and significant changes in the adipokine secretions in comparison to differentiated 3T3-L1 MBX cells maintained in medium without fatty acids. To elucidate the molecular changes associated with adipogenesis and lipid accumulation profile of 3T3-L1 MBX cells, we have also explored the expression of some of the regulatory proteins related to the development and maintenance of adipocytes from the preadipocyte lineage.

Chronic kidney disease (CKD) has become a major global health issue, and abnormalities of glucose metabolism are a risk factor responsible for development of CKD. We aimed to investigate associations between glucose metabolism indices and CKD in a Chinese population and determine which index is superior for predicting incident CKD.

We performed a community-based population on 5232 subjects aged ≥40 years without baseline CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. We examined the associations of glucose metabolism indices, including fasting plasma glucose (FPG), 2-hour (2 h) oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-β and the development of CKD.

With an average follow-up of 3.6 years, 6.4% of the subjects developed CKD. Pearson's correlation analysis revealed that FPG, HbA1c, fasting insulin, and HOMA-IR were all significantly correlated with UACR and eGFR. The association persisted in multivariate linear regression analysis adjusted for age and sex. Compared with other glucose indices, HOMA-IR exhibited the strongest associations with CKD in COX multivariate regression analysis (HR = 1.17, 95% CI: 1.04-1.31).

HOMA-IR is superior to other routine indices of glucose metabolism for predicting the development of CKD in middle-aged Chinese persons. Screening with HOMA-IR may help prevent the development of CKD in the general population.

Bariatric surgery is an appropriate treatment for obese patients with metabolic syndrome. Adipose tissue is an active endocrine tissue secreting leptin and adiponectin that affect body metabolism. Nowadays, a high incidence of metabolic syndrome with an increased risk of serious diseases has been detected in Shiraz. This study aimed to assess the levels of leptin and adiponectin as well as the adiponectin-to-leptin ratio in three different bariatric surgeries among obese patients in Shiraz. The results will play an important role in physicians' choice of surgery by distinguishing the effects of these three bariatric surgeries.

The serum adiponectin and leptin levels were measured using enzyme-linked immunosorbent assay. Blood glucose, lipid profile, weight, and liver enzyme level were measured before and 7 months after surgery.

This clinical trial was conducted on 81 obese patients who underwent sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and single anastomosis sleeve ileal (SASI) bypass surgeries. The results revealed a decrease in fasting blood sugar and triglyceride (TG) levels 7 months after the surgeries. In addition, decrease of body mass index (BMI) was more significantly in the SASI group (12.8 ± 3 4.95) compared to the Roux-en-Y gastric group (8.56 ± 4.61) (P = 0.026). Besides, a more significant improvement in liver function was observed in SG (P < 0.05). Furthermore, the results revealed a significant difference among the three groups regarding the increase in the adiponectin level (P = 0.039). Decrease in the leptin level and increase in the adiponectin level were more significant after the RYGB surgery compared to the SG group (P < 0.05).

The three bariatric surgeries were effective in increasing the adiponectin level and decreasing the leptin levels. The surgeries also changed the metabolic risk factors including TGs, high-density lipoprotein, fasting blood glucose, and BMI.

Temperature changes and periods of detrimental cold occur frequently for many organisms in their natural habitats. Homeothermic animals have evolved metabolic adaptation strategies to increase mitochondrial-based energy expenditure and heat production, largely relying on fat as a fuel source. Alternatively, certain species are able to repress their metabolism during cold periods and enter a state of decreased physiological activity known as torpor. By contrast, poikilotherms, which are unable to maintain their internal temperature, predominantly increase membrane fluidity to diminish cold-related damage from low-temperature stress. However, alterations of molecular pathways and the regulation of lipid-metabolic reprogramming during cold exposure are poorly understood. Here, we review organismal responses that adjust fat metabolism during detrimental cold stress. Cold-related changes in membranes are detected by membrane-bound sensors, which signal to downstream transcriptional effectors, including nuclear hormone receptors of the PPAR (peroxisome proliferator-activated receptor) subfamily. PPARs control lipid metabolic processes, such as fatty acid desaturation, lipid catabolism and mitochondrial-based thermogenesis. Elucidating the underlying molecular mechanisms of cold adaptation may improve beneficial therapeutic cold treatments and could have important implications for medical applications of hypothermia in humans. This includes treatment strategies for hemorrhagic shock, stroke, obesity and cancer.

Adipocytes regulate tissues through production of adipokines that can act both locally and systemically. Adipocytes also have been found to play a critical role in regulating the healing process. To better understand this role, we developed a three-dimensional human adipocyte spheroid system that has an adipokine profile similar to in vivo adipose tissues. Previously, we found that conditioned medium from these spheroids induces human dermal fibroblast conversion into highly contractile, collagen-producing myofibroblasts through a transforming growth factor beta-1 (TGF-β1) independent pathway. Here, we sought to identify how mature adipocytes signal to dermal fibroblasts through adipokines to induce myofibroblast conversion. By using molecular weight fractionation, heat inactivation and lipid depletion, we determined mature adipocytes secrete a factor that is 30-100 kDa, heat labile and lipid associated that induces myofibroblast conversion. We also show that the depletion of the adipokine adiponectin, which fits those physico-chemical parameters, eliminates the ability of adipocyte-conditioned media to induce fibroblast to myofibroblast conversion. Interestingly, native adiponectin secreted by cultured adipocytes consistently elicited a stronger level of α-smooth muscle actin expression than exogenously added adiponectin. Thus, adiponectin secreted by mature adipocytes induces fibroblast to myofibroblast conversion and may lead to a phenotype of myofibroblasts distinct from TGF-β1-induced myofibroblasts.

Metabolic syndrome is a growing epidemic that increases the risk for cardiovascular disease, diabetes, stroke, and mortality. It is diagnosed by the presence of three or more of the following risk factors: 1) obesity, with an emphasis on central adiposity, 2) high blood pressure, 3) hyperglycemia, 4) dyslipidemia, with regard to reduced high-density lipoprotein concentrations, and 5) dyslipidemia, with regard to elevated triglycerides. Smoking is one lifestyle factor that can increase the risk for metabolic syndrome as it has been shown to exert negative effects on abdominal obesity, blood pressure, blood glucose concentrations, and blood lipid profiles. Smoking may also negatively affect other factors that influence glucose and lipid metabolism including lipoprotein lipase, adiponectin, peroxisome proliferator-activated receptors, and tumor necrosis factor-alpha. Some of these smoking-related outcomes may be reversed with smoking cessation, thus reducing the risk for metabolic disease; however, metabolic syndrome risk may initially increase post cessation, possibly due to weight gain. Therefore, these findings warrant the need for more research on the development and efficacy of smoking prevention and cessation programs.

Adipokines are cell-signaling proteins secreted by adipose tissue that has been related to a low-grade state of inflammation and different pathologies. The present review aims to analyze the role of adipokines in health and disease in order to understand the important functions and effects of these cytokines. For this aim, the present review delves into the type of adipocytes and the cytokines produced, as well as their functions; the relations of adipokines in inflammation and different diseases such as cardiovascular, atherosclerosis, mental diseases, metabolic disorders, cancer, and eating behaviors; and finally, the role of microbiota, nutrition, and physical activity in adipokines is discussed. This information would allow for a better understanding of these important cytokines and their effects on body organisms.

Obesity significantly decreases life expectancy and increases the incidence of age-related dysfunctions, including β-cell dysregulation leading to inadequate insulin secretion. Here, we show that diluted plasma from obese human donors acutely impairs β-cell integrity and insulin secretion relative to plasma from lean subjects. Similar results were observed with diluted sera from obese rats fed ad libitum, when compared to sera from lean, calorically restricted, animals. The damaging effects of obese circulating factors on β-cells occurs in the absence of nutrient overload, and mechanistically involves mitochondrial dysfunction, limiting glucose-supported oxidative phosphorylation and ATP production. We demonstrate that increased levels of adiponectin, as found in lean plasma, are the protective characteristic preserving β-cell function; indeed, sera from adiponectin knockout mice limits β-cell metabolic fluxes relative to controls. Furthermore, oxidative phosphorylation and glucose-sensitive insulin secretion, which are completely abrogated in the absence of this hormone, are restored by the presence of adiponectin alone, surprisingly even in the absence of other serological components, for both the insulin-secreting INS1 cell line and primary islets. The addition of adiponectin to cells treated with plasma from obese donors completely restored β-cell functional integrity, indicating the lack of this hormone was causative of the dysfunction. Overall, our results demonstrate that low circulating adiponectin is a key damaging element for β-cells, and suggest strong therapeutic potential for the modulation of the adiponectin signaling pathway in the prevention of age-related β-cell dysfunction.

We examined the effect of a functional milk fat (FMF) on the glucose metabolism and its association with the intramuscular triacylglycerol (TAG) content in rats fed high-fat diets.

Male Wistar rats were fed for 60 days with S7 (soybean oil 7%), S30 (soybean oil 30%), MF30 (soybean oil 3% + milk fat 27%), or FMF30 (soybean oil 3% + FMF 27%) diets. An oral glucose tolerance test was performed. The levels of key metabolites in gastrocnemius muscle and mRNA levels of genes involved in glucose and lipid metabolism in muscle, epididymal white adipose tissue (EWAT), and serum were assessed.

The S30 diet induced glucose intolerance and led to TAG, citrate, and glucose accumulation in muscle. Moreover, we observed a downregulation of uncoupling proteins (Ucp2 and Ucp3) and insulin receptor substrate-1 (Irs1) genes, lower carnitine palmitoyl transferase-1b (CPT-1b), and phosphofructokinase-1 (PFK1) activities in muscle and lower expression of adiponectin (Adipoq) in EWAT. The FMF30 diet ameliorated the glucose intolerance and normalized the glucose and TAG levels in muscle, preventing the accumulation of citrate and enhancing glucose utilization by the PFK1. The beneficial effects might also be related to the higher expression of Adipoq in EWAT, its receptor in muscle (Adipor1), and the expression of Ucp2, Ucp3, and Irs1 in muscle, restoring the alterations observed with the S30 diet.

FMF30 modulated key genes involved in glucose and lipid metabolism in skeletal muscle, improving the glucose utilization and preventing TAG, glucose, and citrate accumulation.

Adiponectin, one of the most ubiquitous adipokines found in the blood, plays a major role in glucolipid metabolism and energy metabolism and regulation. In recent years, a growing body of research indicates that adiponectin also plays a significant role in diabetic retinopathy. In the present review, we specifically address the protective effects of adiponectin on the development and progression of diabetic retinopathy through improvement in insulin resistance, alleviation of oxidative stress, limiting of inflammation, and prevention of vascular remodeling, with the aim to explore new potential approaches and targets for the prevention and treatment of diabetic retinopathy.

Arbutin is a glycosylated hydroquinone with antioxidant and anti-hyperglycemia effects. However, its beneficial effects in type 2 diabetes (T2D) were not clarified. This study evaluated the effect of arbutin on hyperglycemia, dyslipidemia, insulin resistance, oxidative stress, and inflammatory response in T2D. Rats induced by high fat diet and streptozotocin were treated with arbutin (25 and 50 mg/kg for 4 weeks). Diabetic rats exhibited glucose intolerance, elevated HbA1c%, reduced insulin, and high HOMA-IR. Liver glycogen and hexokinase activity were decreased in T2D rats while glucose-6-phosphatase (G6Pase), fructose-1,6- biphosphatase (FBPase), and glycogen phosphorylase were upregulated. Circulating and hepatic cholesterol and triglycerides and serum transaminases were elevated in T2D rats. Arbutin ameliorated hyperglycemia, dyslipidemia, insulin deficiency and resistance, and liver glycogen and alleviated the activity of carbohydrate-metabolizing enzymes. Both doses of arbutin decreased serum transaminases and resistin, and liver lipids, TNF-α, IL-6, malondialdehyde and nitric oxide, downregulated liver resistin and fatty acid synthase, and increased serum and liver adiponectin, and liver reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). These effects were associated with the upregulation of hepatic PPARγ. Arbutin inhibited α-glucosidase in vitro and in silico investigations revealed the ability of arbutin to bind PPARγ, hexokinase, and α-glucosidase. In conclusion, arbutin effectively ameliorated glucose intolerance, insulin resistance, dyslipidemia, inflammation, and oxidative stress, and modulated carbohydrate-metabolizing enzymes, antioxidants, adipokines and PPARγ in T2D in rats.

Adiponectin has been demonstrated to be a mediator of insulin sensitivity; however, the underlined mechanisms remain unclear. SESN2 is a stress-inducible protein that phosphorylates AMPK in different tissues. In this study, we aimed to validate the amelioration of insulin resistance by globular adiponectin (gAd) and to reveal the role of SESN2 in the improvement of glucose metabolism by gAd. We used a high-fat diet-induced wild-type and SESN2-/- C57BL/6J insulin resistance mice model to study the effects of six-week aerobic exercise or gAd administration on insulin resistance. In vitro study, C2C12 myotubes were used to determine the potential mechanism by overexpressing or inhibiting SESN2. Similar to exercise, six-week gAd administration decreased fasting glucose, triglyceride and insulin levels, reduced lipid deposition in skeletal muscle and reversed whole-body insulin resistance in mice fed on a high-fat diet. Moreover, gAd enhanced skeletal muscle glucose uptake by activating insulin signaling. However, these effects were diminished in SESN2-/- mice. We found that gAd administration increased the expression of SESN2 and Liver kinase B1 (LKB1) and increased AMPK-T172 phosphorylation in skeletal muscle of wild-type mice, while in SESN2-/- mice, LKB1 expression was also increased but the pAMPK-T172 was unchanged. At the cellular level, gAd increased cellular SESN2 and pAMPK-T172 expression. Immunoprecipitation experiment suggested that SESN2 promoted the formation of complexes of AMPK and LKB1 and hence phosphorylated AMPK. In conclusion, our results revealed that SESN2 played a critical role in gAd-induced AMPK phosphorylation, activation of insulin signaling and skeletal muscle insulin sensitization in mice with insulin resistance.

Adiponectin (ADIPOQ) is a member adipocytokines, and its actions are supported by two receptors, ADIPOQ receptor 1 and -2, respectively (ADIPOR1 and -R2). Our study was performed to evaluate the ADIPOR1 presence and location and its gene expression in reproductive tissues of the male ram, during its non-breading season. The different portions of the male ram reproductive system (testis, epididymis, seminal vesicle, ampoule vas deferens, bulb-urethral gland) were collected in a slaughterhouse. Immunohistochemistry showed ADIPOR1 positive signals in the cytoplasm of all the glandular epithelial cells, with a location near the nucleus; in the testes, the positive reaction was evidenced in the cytoplasm in the basal portion of the germinal epithelial cells. The immune reaction intensity was highest (p < 0.001) in the prostate and seminal vesicles glands than that of other parts of the ram reproductive tract. RT-qPCR detected the ADIPOR1 transcript in the testes, epididymis, vas deferens, bulbourethral glands, seminal vesicles, and prostate; the expression levels were high (p < 0.01) in the prostate and low (p < 0.01) in the testis, epididymis, and bulbourethral glands. The present results evidenced the possible ADIPOQ/ADIPOR1 system's role in regulating the testicular activity of male rams during the non-breading season.

The alteration of signaling molecules involved in the general metabolism of animals can negatively influence reproduction. In dairy cattle, the development of follicular cysts and the subsequent appearance of ovarian cystic disease (COD) often lead to decreased reproductive efficiency in the herd. The objective of this review is to summarize the contribution of relevant metabolic and nutritional sensors to the development of COD in dairy cows. In particular, we focus on the study of alterations of the insulin signaling pathway, adiponectin, and other sensors and metabolites relevant to ovarian functionality, which may be related to the development of follicular persistence and follicular formation of cysts in dairy cattle. The results of these studies support the hypothesis that systemic factors could alter the local scenario in the follicle, generating an adverse microenvironment for the resumption of ovarian activity and possibly leading to the persistence of follicles and to the development and recurrence of COD.

Cd248 has recently been associated with adipose tissue physiology, demonstrated by reduced weight gain in high fat diet-fed mice with genetic deletion of Cd248 relative to controls. Here we set out to determine the metabolic consequences of loss of Cd248. Strikingly, we find these to be sex specific; By subjecting Cd248-/- and Cd248+/+ mice to a high fat diet and indirect calorimetry study, we identified that only male Cd248-/- mice show reduced weight gain compared to littermate control wildtype mice. In addition, male (but not female) mice showed a lower respiratory exchange ratio on both chow and high fat diets, indicating a predisposition to metabolise lipid. Lipidomic studies on specific fat depots found reduced triglyceride and diglyceride deposition in male Cd248-/- mice, and this was supported by reduced expression of lipogenic and adipogenic genes. Finally, metabolomic analysis of isolated, differentiated preadipocytes found alterations in metabolic pathways associated with lipid deposition in cells isolated from male, but not female, Cd248-/- mice. Overall, our results highlight the importance of sex controls in animal studies and point to a role for Cd248 in sex- and depot-specific regulation of lipid metabolism.

Adiponectin is an abundant adipocytokine secreted by adipocytes. It exists in the plasma in its trimeric, hexameric, high-molecular-weight (HMW), and globular (a proteolytic product) isoforms. Adiponectin's anti-inflammatory effects on macrophages remain controversial. We have previously reported a simple and effective method for purifying native HMW adiponectin from human plasma. Here, we investigated whether native HMW adiponectin from human plasma has anti-inflammatory effects on macrophages. Pretreatment with human native HMW adiponectin inhibited lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β) gene expression, but not tumor necrosis factor (TNF)-α expression. However, simultaneous treatment with HMW adiponectin and LPS did not inhibit IL-1β expression. Further, HMW adiponectin pretreatment decreases glycogen synthase kinase-3β (GSK-3β) inactivation by abrogating LPS-induced Akt (Ser473) phosphorylation, which subsequently suppresses LPS-induced CCAAT/enhancer binding protein β (C/EBPβ) protein translation and nuclear translocation. However, HMW adiponectin pretreatment did not affect LPS-induced nuclear factor-kappaB (NF-κB) activation. These results suggest that HMW adiponectin mediates potent anti-inflammatory activities in macrophages by inhibiting its Akt-C/EBPβ signaling pathway, thereby suppressing IL-1β gene expression.

Pituitary adenomas have recently become more common and their incidence is increasing yearly. Functional pituitary tumors commonly secrete prolactin, growth hormones, and adrenocorticotropic hormones, which cause diseases such as prolactinoma, acromegaly, and Cushing's disease, but rarely secrete luteinizing, follicle-stimulating, thyroid-stimulating, and melanocyte-stimulating hormones. In addition to the typical clinical manifestations of functional pituitary tumors caused by excessive hormone levels, some pituitary tumors are also accompanied by abnormal glucose metabolism. The effects of these seven hormones on glucose metabolism are important for the treatment of diabetes secondary to pituitary tumors. This review focuses on the effects of hormones on glucose metabolism, providing important clues for the diagnosis and treatment of related diseases.

Increasing adipogenesis has been explored to treat metabolic diseases and atherosclerosis through the release of adiponectin. The effects and mechanism of platelet-rich plasma treatment on fat graft survival and adipogenesis have not been clarified. Here, we aimed to study the effects of monocyte chemoattractant protein-1 (MCP-1)-supplemented plasma on adipogenesis-related gene expression and adiponectin levels. Stromal vascular fractions (SVFs) purified from the inguinal adipose tissue of obese and diabetic (Lepr^db/db) mice were treated with plasma from control (Lepr^+/+) mice supplemented with 10 or 50 ng of MCP-1. The expression of adiponectin and interleukin-33 (IL-33) mRNA in adipose tissue was increased in Lepr^db/db mice, whereas control (Lepr^+/+) plasma reduced expression of IL-33 mRNA as well as peroxisome proliferator-activated receptor gamma (PPARγ), pJNK, and pNF-κB protein, and increased the expression of IL-10 mRNA in SVFs of Lepr^db/db mice. MCP-1-supplemented control plasma increased the expression of adiponectin, CCAAT-enhancer-binding protein α (C/EBPα), dipeptidyl peptidase 4 (DPP4), IL-33, and PDGFα mRNA and the expression of adiponectin protein as well as PPARγ of SVFs and the expression of PPARγ mRNA in adipose tissue macrophages (ATMs). Injection of MCP-1-supplemented plasma into adipose tissue of Lepr^db/db mice increased the expression of IL-33 and Col3a1 mRNA in SVFs and IL-33, FABP4, PDGFα, PPARγ and PPARγ2 of ATMs, protein expression of adiponectin and PPARγ of SVFs, and plasma adiponectin levels, as well as DPP4 activity. In conclusion, our results demonstrate that control plasma decreases adipogenesis and increases IL-10, and decreases IL-33, pJNK, and pNF-κB in adipose tissue. MCP-1-supplemented plasma enhances adipogenesis-related gene expression in SVFs and adiponectin levels, which may be mediated through an increase of IL-33 and PPARγ. Thus, our findings suggest that MCP-1-supplemented plasma represents a novel therapy to stimulate local adipogenesis and systemic adiponectin levels.

A decrease in the circulating levels of adiponectin in obesity increases the risk of metabolic complications, but the role of globular adiponectin, a truncated form produced by proteolytic cleavage, has not been defined. The objective of this investigation was to determine how globular adiponectin is generated and to determine whether this process impacts obesity. The cleavage of recombinant full-length adiponectin into globular adiponectin by plasma in vitro was used to identify Gly-93 as the N-terminal residue after proteolytic processing. The amino acid sequence of the cleavage site suggested thrombin was the protease responsible for cleavage, and inhibitors confirmed its likely involvement. The proteolytic site was modified, and this thrombin-resistant mutant protein was infused for 4 weeks into obese adiponectin-knockout mice that had been on a high-fat diet for 8 weeks. The mutation of the cleavage site ensured that globular adiponectin was not generated, and thus did not confound the actions of the full-length adiponectin. Mice infused with the mutant adiponectin accumulated less fat and had smaller adipocytes compared to mice treated with globular adiponectin, and concurrently had elevated fasting glucose. The data demonstrate that generation of globular adiponectin through the action of thrombin increases both adipose tissue mass and adipocyte size, but it has no effect on fasting glucose levels in the context of obesity.