AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: Implications for obesity

MicroRNA-33–dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis

“…Consistent with this, we identify a major role for miR-33 targeting of AMPK, a master metabolic switch, in mediating its effects on macrophage inflammation. AMPK increases FAO via a 2-pronged mechanism: (a) inhibitory phosphorylation and inhibition of acetyl-CoA carboxylase, lowering malonyl-CoA-mediated inhibition of CPT1 and stimulating uptake of activated fatty acids into the mitochondria (44,45), and (b) enhancement of expression of SIRT1 and PGC-1α, resulting in transcriptional activation of genes involved in mitochondrial FAO and mitochondrial biogenesis (46,47). Mechanistically, we show that miR-33 overexpression reduces cellular oxygen consumption and increases extracellular acidification indicative of increased glycolysis, which is paralleled by an increase in markers of M1 macrophages (e.g., Il1b, Il6, Nos2) in WT, but not AMPK-deficient, macrophages.…”

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

“…ACC2 produces malonyl CoA, an allosteric inhibitor of the key enzyme carnitine palmitoyltransferase 1 (CPT1), which controls the entry of FAs into the mitochondria for oxidation (Hardie & Pan 2002). The pharmacological activation of AMPK has been shown to produce changes in muscle metabolic pathway capacity similar to those produced by exercise training (O'Neill et al 2013); however, there is considerable controversy as to whether AMPK activation can drive energy expenditure in the absence of exercise. A series of studies employing genetic deletion of Acc2 (Acacb) have reported reduced fat depots in association with increased FA oxidation in isolated muscle (Abu-Elheiga et al 2001, 2003 and have subsequently reported increased energy expenditure (although not increased FA oxidation) in Acc2-knockout mice with less fat and less lean mass ).…”

Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis

“…Accordingly, the plant-derived alkaloid berberine or microRNA-455 enhances brown adipogenesis via activation of AMPK (26,27). In addition, AMPK stimulates glycolysis (28) and coupled respiration-mediated ATP generation in metabolic tissues (29)(30)(31). Hence, the AMPK activator 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR) stimulates EE (32,33).…”