(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