Haptoglobin (Hp) is a hemoglobin-binding acute-phase serum protein. Several single nucleotide variations (SNVs) within the Hp gene (HP) or Hp-related protein gene (HPR), such as rs5471 (A > C) and rs5472 (A > G) in HP promoter region and rs2000999 (G > A) in intron 2 of HRP, are suggested to correlate with the serum Hp levels. To determine these three SNVs simultaneously, a genotyping assay based on duplex dual-labeled fluorescent probes was developed. The method was then validated by analyzing genomic DNA from 121 Ghanaian and two Japanese subjects who had been previously genotyped for rs5471, rs5472, and rs2000999. Both rs5471 and rs5472 could be determined as haplotypes with a single FAM-labeled fluorescent probe, and rs2000999 could be genotyped with a HEX-labeled fluorescent probe. The results obtained with the present method were consistent with the previous results except for those of three Ghanaian subjects. All three subjects appear to have multiple HPR copy number variants characteristic of African populations, which may have led to incorrect results during previous genotyping. This method allows us to genotype these three SNVs in a relatively large number of samples, especially in African populations where rs5471 is uniquely distributed.

Depression and obesity are associated with impaired inhibitory control. Behavioral evidence indicates an exacerbating additive effect when both conditions co-occur. However, the underlying neural mechanisms remain unclear. Moreover, systemic inflammation affects neurocognitive performance in both individuals with depression and obesity. Here, we investigate additive effects of depression and obesity on neural correlates of inhibitory control, and examine inflammation as a connecting pathway.

We assessed inhibitory control processing in 64 individuals with obesity and varying degrees of depressed mood by probing neural activation and connectivity during an fMRI Stroop task. Additionally, we explored associations of altered neural responses with individual differences in systemic inflammation. Data were collected as part of the BARICO (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity) study.

Concurrent depression and obesity were linked to increased functional connectivity between the supplementary motor area and precuneus and between the inferior occipital and inferior parietal gyrus. Exploratory analysis revealed that circulating inflammation markers, including plasma leptin, IL-6, IL-8, and CCL-3 correlated with the additive effect of depression and obesity on altered functional connectivity.

The observational design limits causal inferences. Future research employing longitudinal or intervention designs is required to validate these findings and elucidate causal pathways.

These findings suggest increased neural crosstalk underlying impaired inhibitory control in individuals with concurrent obesity and depressed mood. Our results support a model of an additive detrimental effect of concurrent depression and obesity on neurocognitive functioning, with a possible role of inflammation.

Gestational diabetes mellitus (GDM) is the most frequent metabolic alteration in pregnancy. Several abnormalities in visceral adipose tissue (VAT) have been described as part of its pathophysiology including hypertrophy, inflammation and altered lipid metabolism. Farnesoid X receptor (FXR) is involved in adipocyte physiology and inflammation, so its expression may correlate with the expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lipoprotein lipase (LPL), and two fatty acid transporters (SLC27A2, and SLC27A4).

To compare the FXR, LPL, SLC27A2, SLC27A4, TNF-α, and IL-10 mRNA expression in VAT between women with GDM and healthy pregnant (HP) women. Secondarily, to evaluate the potential correlation between these expression levels.

Cross-sectional study of 50 GDM and 50 HP women. Conventional biochemical tests were performed and relative mRNA expression in VAT was measured by RT-qPCR.

Gene expression levels of FXR and IL-10 were lower, whereas those of LPL, as well as the TNF-α/IL-10 ratio, were higher in women with GDM compared to HP. Pre-pregnancy BMI was the main significant independent variable for FXR levels in VAT from women with GDM. In all women, LPL expression levels correlated positively with those of SLC27A2. Only in women with GDM, IL-10 expression levels correlated negatively with those of SLC27A2, and SLC27A4.

GDM is associated with decreased expression of FXR and IL-10 and increased expression of LPL, as well as a higher TNF/IL-10 ratio in VAT. These results suggest increased lipid storage and pro-inflammatory state indicating VAT dysfunction in this metabolic disorder.

In patients with non-alcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM), alpha-2 macroglobulin (A2M), apolipoprotein A1 (ApoA1), and haptoglobin are associated with the risk of liver fibrosis, inflammation (NASH), and COVID-19. We assessed if these associations were worsened by T2DM after adjustment by age, sex, obesity, and COVID-19. Three datasets were used: the “Control Population”, which enabled standardization of protein serum levels according to age and sex (N = 27,382); the “NAFLD-Biopsy” cohort for associations with liver features (N = 926); and the USA “NAFLD-Serum” cohort for protein kinetics before and during COVID-19 (N = 421,021). The impact of T2DM was assessed by comparing regression curves adjusted by age, sex, and obesity for the liver features in “NAFLD-Biopsy”, and before and during COVID-19 pandemic peaks in “NAFLD-Serum”. Patients with NAFLD without T2DM, compared with the values of controls, had increased A2M, decreased ApoA1, and increased haptoglobin serum levels. In patients with both NAFLD and T2DM, these significant mean differences were magnified, and even more during the COVID-19 pandemic in comparison with the year 2019 (all p < 0.001), with a maximum ApoA1 decrease of 0.21 g/L in women, and a maximum haptoglobin increase of 0.17 g/L in men. In conclusion, T2DM is associated with abnormal levels of A2M, ApoA1, and haptoglobin independently of NAFLD, age, sex, obesity, and COVID-19.

Haptoglobin (Hp) is an acidic glycoprotein, existing in the serum and other body fluids of human beings and a variety of mammals. Hp is produced in the liver, white adipose tissue, and the kidney. The genetic polymorphisms and different phenotypes of Hp have different biological functions. Hp has antibacterial, antioxidant, and angiogenic effects and is associated with multiple diseases including simple obesity, vascular complications of diabetes mellitus, nonalcoholic fatty liver disease, hypertension, blood diseases, autoimmune diseases, and malignant tumors. Hp also participates in many life activities, indicating the importance of Hp in further studies. Previously, we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials. However, the specific mechanism of Hp in patients with simple obesity is still unclear. The purpose of this article is to introduce recent research progress on Hp, emphasizing the relationship between Hp and the development of metabolic disease, which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.

Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.