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. 2023 Oct 28;15(10):e47875. doi: 10.7759/cureus.47875

Figure 1. Seven epigenetic mechanisms of obesity.

Figure 1

(1) Obesity induced hypomethylation of leptin gene leading to ­leptin release, increased stimulation of POMC neurons and MSH release, ­increased stimulation of neurons expressing MC4R, increased appetite suppression to decrease energy intake; (2) Demethylation of ILGF2 gene leading to increased ILGF2 levels, increased ILGF1 receptor stimulation and increased adipogenesis; (3) Hypomethylation of NPY genes leads to increased NPY release, increased hunger and a tendency to over-eat; (4) HFD leads to decreased acetylation of POMC resulting in decreased POMC release and decreased appetite suppression; (5) HFD leads to increased acetylation of NPY resulting in increased NPY release, increased hunger and a tendency to over-eat; (6) HFD leads to increased acetylation of TNF-alpha, increased TNFalpha expression, insulin resistance and increased adipogenesis and lipid storage; (7) HFD leads to increased methylation of PPAR-gamma, decreased PPAR-gamma expression, insulin resistance and increased adipogenesis and lipid storage.

ILGF2=insulin like growth factor 2; ILGF1=insulin like growth factor 1; POMC=pro-opiomelanocortin; MSH=melanocytes stimulating hormone, MC4R=melanocortin-4 receptor; NPY=neuropeptide Y, HFD=high-fat diet; TNF-alpha=tumor necrosis factor alpha; PPAR-gamma=peroxisome proliferator-activated receptor gamma

Image credit: Erin N.L. Smith