Malic Enzyme 1 (ME1) Promotes Adiposity and Hepatic Steatosis and Induces Circulating Insulin and Leptin in Obese Female Mice

Abstract

Malic Enzyme 1 (ME1) supports lipogenesis, cholesterol synthesis, and cellular redox potential by catalyzing the decarboxylation of L-malate to pyruvate, and the concomitant reduction of NADP to NADPH. We examined the contribution of ME1 to the development of obesity by provision of an obesogenic diet to C57BL/6 wild type (WT) and MOD-1 (lack ME1 protein) female mice. Adiposity, serum hormone levels, and adipose, mammary gland, liver, and small intestine gene expression patterns were compared between experimental groups after 10 weeks on a diet. Relative to WT female mice, MOD-1 female mice exhibited lower body weights and less adiposity; decreased concentrations of insulin, leptin, and estrogen; higher concentrations of adiponectin and progesterone; smaller-sized mammary gland adipocytes; and reduced hepatosteatosis. MOD-1 mice had diminished expression of Lep gene in abdominal fat; Lep, Pparg, Klf9, and Acaca genes in mammary glands; Pparg and Cdkn1a genes in liver; and Tlr9 and Ffar3 genes in the small intestine. By contrast, liver expression of Cdkn2a and Lepr genes was augmented in MOD-1, relative to WT mice. Results document an integrative role for ME1 in development of female obesity, suggest novel linkages with specific pathways/genes, and further support the therapeutic targeting of ME1 for obesity, diabetes, and fatty liver disease.

Proteomic and metabolomic analysis of GH deficiency-induced NAFLD in hypopituitarism: insights into oxidative stress

“…Several studies have shown that ME1 may be involved in adiposity and hepatic steatosis. For example, a study in rats with ME1 deficiency found that ME1 may promote adiposity and hepatic steatosis and induce circulating insulin and leptin, supporting the therapeutic targeting of ME1 for obesity, diabetes, and hepatic steatosis ( 55 , 56 ).…”

Investigating the impact of various fat supplements and their levels on the expression of lipid metabolism-regulated genes in the liver tissue of broiler chickens

“…This cofactor has a significant impact on the synthesis of fatty acids. ME1 actively participates in lipogenesis and maintains the delicate equilibrium between glucose and fatty acid metabolism (37). In a recent investigation by Leng et al in 2019, the researchers aimed to examine the influence of dietary fat supplementation on the expression of ME1 in the liver of broiler chickens.…”

Alternative Polyadenylation of Malic Enzyme 1 Is Essential for Accelerated Adipogenesis

“…The amount of NADPH required for biosynthesis accounts for more than 80% of the total intracellular NADPH, while most of the NADHP used for biosynthesis is used to synthesize fatty acids . NADPH produced through the series of catalytic reactions of ME1 is mainly used in biosynthesis, such as lipogenesis and cholesterol synthesis . Previous studies have found that most of the NADPH required for adipogenesis in 3T3-L1 cells is provided by ME1 .…”

“…41 NADPH produced through the series of catalytic reactions of ME1 is mainly used in biosynthesis, such as lipogenesis and cholesterol synthesis. 42 Previous studies have found that most of the NADPH required for adipogenesis in 3T3-L1 cells is provided by ME1. 31 Considering the role of ME1 in adipogenesis, its expression may be regulated at multiple levels.…”