Pathogenic analysis of post-transplantation obesity: A comprehensive systematic review

Table 6 Molecular pathways and key factors in transplant-associated adipogenesis

Mechanism type	Specific ways	Key molecules/factors	Effect
Inflammatory cascade activates adipogenic pathways	Activation of signaling pathways[40,41]	NF-Kb, JAK/STAT, TNF-α, SIRT1, PPARy, C/EBPα	Inflammatory signaling activates NF-κB, JAK/STAT pathways, TNF-α enhances PPARV activity by inhibiting SIRT1 or promoting its phosphorylation and up-regulation of key adipogenic transcription factors drives preadipocyte differentiation
	Epigenetic regulation[36,42]	IL-6, DNMT, Pref-1	Activation of DNMT by IL-6 and inhibition of Pref-1 release the suppression of adipogenesis and alteration of adipogenesis-related gene expression by epigenetic mechanisms
	Extracellular matrix effects[34,35]	Integrin signaling pathway ECM components	Inflammation leads to extracellular matrix sclerosis, which promotes proliferation and differentiation of adipocyte precursors through activation of mechanotransduction by the integrin signaling pathway; aberrant deposition of ECM components regulates adipocyte-matrix interactions and affects adipogenic efficiency
Oxidative stress activates adipogenic pathways	Transcription factor activation[33,38]	ROS, Nrf2, SREBP-1c	ROS activate redox-sensitive transcription factors such as Nrf2, which binds to the SREBP.1c promoter under chronic oxidative stress to directly promote adipogenic gene transcription
	lipid peroxidation[33,38]	4-Hydroxynonenal, ACC, FAS	Oxidative stress leads to lipid peroxidation to generate aldehyde products, and modification of sulfhydryl groups of key adipogenic proteins, such as ACC. FAS, alters their enzymatic activity or stability and promotes lipid synthesis
	Metabolic reprogramming[32,37]	mitochondrial membrane potential, ATP, Acetyl Coenzyme A, AMPK/mTOR pathway	Oxidative stress induces the loss of mitochondrial membrane potential, ATP synthesis decreases cellular energy metabolism from oxidative phosphorylation to glycolysis, increases the generation of acetyl-coenzyme A, which provides substrates for fat synthesis, and at the same time activates the AMPK/mTOR pathway to promote the proliferation and differentiation of adipocyte precursors
Inflammation and oxidative stress synergize	Signal network synergy[33,39]	ROS, IKK complex, NF-κB, TNF-α, NLRP3inflammatory, vesicle	ROS activate IKK complex, promote NFKB nuclear translocation, and up-regulate inflammatory cytokines and adipogenic gene expression: TNF-α induces mitochondrial ROS production, and ROS activate NLRP3 inflammatory vesicles, forming a positive feedback loop and continuously activating the adipogenic pathway

TNF-α: Tumor necrosis factor-alpha; SIRT1: Sirtuin 1; C/EBPα: CCAAT/enhancer-binding protein alpha; IL-6: Interleukin-6; DNMT: DNA methyltransferase; Pref-1: Preadipocyte factor-1; ECM: Extracellular matrix; ROS: Reactive oxygen species; Nrf2: Nuclear factor erythroid 2–related factor 2; SREBP-1c: Sterol regulatory element-binding protein 1c; ACC: Acetyl-CoA carboxylase; FAS: Fatty acid synthase; AMPK: AMP-activated protein kinase; mTOR: Mechanistic target of rapamycin; IKK: IκB kinase; NLRP3: NLR family pyrin domain containing 3.