Infusion of a Lipid Emulsion Modulates AMPK and Related Proteins in Rat Liver, Muscle, and Adipose Tissues

Abstract

The primary objective of this study was to investigate the impact of lipid oversupply on the AMPK pathway in skeletal muscle, liver, and adipose tissue. Male Wistar rats were infused with lipid emulsion (LE) or phosphate-buffered saline for 5 h/day for 6 days. Muscles exposed to LE for 6 days exhibited increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, along with a greater association between AMPK and Ca 2+ /calmodulin-dependent protein kinase kinase (CaMKK). No differences in muscle protein phosphatase 2C (PP2C) activity, LKB1 phosphorylation or AMPK and LKB1 association were observed. Muscle ACCβ, and adiponectin receptor 1 (AdipoR1) mRNA levels and PPARγ-co-activator 1α (PGC1α) protein levels were also increased in LE-treated rats. In contrast, AMPK and ACC phosphorylation decreased and PP2C activity increased in rat livers exposed to LE. Hepatic mRNA levels of ACCα, PPARα, AdipoR1, AdipoR2, and sterol regulatory element-binding protein-1c (SREBP1c) were also reduced after LE infusion. In adipose tissue, there was no significant alteration in AMPK or ACC phosphorylation. These results demonstrate that following lipid oversupply the AMPK pathway was enhanced in rat skeletal muscle while diminished in the liver and was unchanged in adipose tissue. CaMKK in skeletal muscle and PP2C in the liver, at least in part, appear to mediate these alterations. Alterations in AMPK pathway in the liver induced metabolic defects associated with lipid oversupply.

Dietary Capsaicin Attenuates Metabolic Dysregulation in Genetically Obese Diabetic Mice

“…In liver, adiponectin binds mainly to membrane-bound AdipoR2 and activates AMPK and peroxisome proliferation-activated receptor a pathways, leading to reductions in acetyl-coenzyme A carboxylase and fatty acid synthase activities and induction of carnitine palmitoyl transferase I activity, thereby increasing oxidation of nonesterified fatty acids and decreasing de novo lipogenesis. 19 We observed that hepatic AMPK activation increased in the capsaicin-supplemented mice; this presumably reflected the decrease in hepatic triglyceride content and led to the decreased fatty liver formation. Given the increase in the systemic levels of adiponectin and of AdipoR2 in liver, the decreased hepatic fat accumulation with dietary capsaicin may be attributed to stimulation of adiponectin action via its interaction with AdipoR2.…”

Increasing Dietary Fat Elicits Similar Changes in Fat Oxidation and Markers of Muscle Oxidative Capacity in Lean and Obese Humans

“…How increasing fat intake affects this network in skeletal muscle is not completely understood. Although studies in rodent models have shown increases in SIRT1, AMPK, and PGC1- α mRNA and protein in response to high fatty acid loads [29], [30], [31], [32], a study in lean humans reported a decrease in the mRNA of PGC1- α and other genes associated with oxidative capacity in response to an increase in dietary fat intake [33]. To our knowledge, only one study has compared the molecular adaptations to a HF diet in lean and obese humans [34].…”

The Mechanisms Underlying Lipid Resuscitation Therapy

“…124,125 Lipid also modifies signaling in many pathways while functioning as a metabolic fuel. Lipid activates Akt, Erk1/2, and GSK-3b after IR injury, 112,[116][117][118] as well as AMPK in peripheral tissues, 126 and can drive cardiac hypertrophy. 127 Long-term lipid treatment activates PKCy and PKCδ via diacylglycerol to promote insulin resistance.…”