Sucrose-Enriched and Carbohydrate-Free High-Fat Diets Distinctly Affect Substrate Metabolism in Oxidative and Glycolytic Muscles of Rats.

Skeletal muscle substrate preference for fuel is largely influenced by dietary macronutrient availability. The abundance of dietary carbohydrates promotes the utilization of glucose as a substrate for energy production, whereas an abundant dietary fat supply elevates rates of fatty acid (FA) oxidation. The objective of this study was to determine whether an obesogenic, high-fat, sucrose-enriched (HFS) diet or a carbohydrate-free ketogenic diet (KD) exert distinct effects on fat, glucose, and ketone metabolism in oxidative and glycolytic skeletal muscles.

A high-fat diet supplemented with medium-chain triglycerides ameliorates hepatic steatosis by reducing ceramide and diacylglycerol accumulation in mice.

Non-alcoholic fatty liver disease (NAFLD) is projected to be the most common chronic liver disease worldwide and is closely linked to obesity, insulin resistance and type 2 diabetes. Currently, no pharmacological treatments are available to treat NAFLD, and lifestyle modification, including dietary interventions, is the only remedy. Therefore, we conducted a study to determine whether supplementation with medium-chain triglycerides (MCTs), containing a mixture of C8 and C10 (60/40), attenuates NAFLD in obese and insulin-resistant mice.

Glucagon-like peptide-1 receptor activation stimulates PKA-mediated phosphorylation of Raptor and this contributes to the weight loss effect of liraglutide.

The canonical target of the glucagon-like peptide-1 receptor (GLP-1R), Protein Kinase A (PKA), has been shown to stimulate mechanistic Target of Rapamycin Complex 1 (mTORC1) by phosphorylating the mTOR-regulating protein Raptor at Ser following β-adrenergic stimulation. The objective of these studies is to test whether GLP-1R agonists similarly stimulate mTORC1 via PKA phosphorylation of Raptor at Ser and whether this contributes to the weight loss effect of the therapeutic GLP-1R agonist liraglutide. We measured phosphorylation of the mTORC1 signaling target ribosomal protein S6 in Chinese Hamster Ovary cells expressing GLP-1R (CHO-Glp1r) treated with liraglutide in combination with PKA inhibitors.

Gβγ-SNAP25 exocytotic brake removal enhances insulin action, promotes adipocyte browning, and protects against diet-induced obesity.

Negative regulation of exocytosis from secretory cells is accomplished through inhibitory signals from Gi/o GPCRs by Gβγ subunit inhibition of 2 mechanisms: decreased calcium entry and direct interaction of Gβγ with soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) plasma membrane fusion machinery. Previously, we disabled the second mechanism with a SNAP25 truncation (SNAP25Δ3) that decreased Gβγ affinity for the SNARE complex, leaving exocytotic fusion and modulation of calcium entry intact and removing GPCR-Gβγ inhibition of SNARE-mediated exocytosis. Here, we report substantial metabolic benefit in mice carrying this mutation.