sodium-lactate and Insulin-Resistance

Increased production of very low-density lipoprotein (VLDL) is a critical feature of the metabolic syndrome. Here we report that a selective increase in brain glucose lowered circulating triglycerides (TG) through the inhibition of TG-VLDL secretion by the liver. We found that the effect of glucose required its conversion to lactate, leading to activation of ATP-sensitive potassium channels and to decreased hepatic activity of stearoyl-CoA desaturase-1 (SCD1). SCD1 catalyzed the synthesis of oleyl-CoA from stearoyl-CoA. Curtailing the liver activity of SCD1 was sufficient to lower the hepatic levels of oleyl-CoA and to recapitulate the effects of central glucose administration on VLDL secretion. Notably, portal infusion of oleic acid restored hepatic oleyl-CoA to control levels and negated the effects of both central glucose and SCD1 deficiency on TG-VLDL secretion. These central effects of glucose (but not those of lactate) were rapidly lost in diet-induced obesity. These findings indicate that a defect in brain glucose sensing could play a critical role in the etiology of the metabolic syndrome.

Topics: Animals; Blotting, Western; Brain; DNA Primers; Dose-Response Relationship, Drug; Glucose; Insulin; Insulin Resistance; Lipoproteins, VLDL; Liver; Male; Metabolic Syndrome; Obesity; Oxamic Acid; Rats; Rats, Sprague-Dawley; Sodium Lactate; Somatostatin; Stearoyl-CoA Desaturase; Triglycerides