Chronic intranasal insulin does not affect hepatic lipids but lowers circulating BCAAs in healthy male subjects

Context: Nonalcoholic fatty liver disease and elevated circulating branched-chain amino acids (BCAAs) are common characteristics of obesity and type 2 diabetes. In rodents, brain insulin signaling controls both hepatic triglyceride secretion and BCAA catabolism. Whether brain insulin signaling controls similar metabolic pathways in humans is unknown. Objective: Here we assessed if intranasal insulin, a method to preferentially deliver insulin to the central nervous system, is able to modulate hepatic lipid content and plasma BCAAs in humans. Design/Setting: We conducted a randomized, double-blind, placebo-controlled trial at the Medical University of Vienna. Participants/Intervention: We assessed if a chronic 4-week intranasal insulin treatment (40 IU, 4 times daily) reduces hepatic triglyceride content and circulating BCAAs in 20 healthy male volunteers. Main Outcome Measures: Hepatic lipid content was assessed noninvasively by 1H-magnetic resonance spectroscopy, and BCAAs were measured by gas chromatography mass spectrometry at defined time points during the study. Results: Chronic intranasal insulin treatment did not alter body weight, body mass index, and hepatic lipid content but reduced circulating BCAA levels. Conclusions: These findings support the notion that brain insulin controls BCAA metabolism in humans. Thus, brain insulin resistance could account at least in part for the elevated BCAA levels observed in the insulin-resistant state.