Apolipoprotein A-IV is induced by high-fat diets and mediates positive effects on glucose and lipid metabolism

Apolipoprotein A-IV is induced by high-fat diets and mediates positive effects on glucose and lipid metabolism

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Objective: Low-carbohydrate, high-fat diets under eucaloric rb3519 replacement lenses conditions are associated with several health-beneficial metabolic effects in humans, particularly in the liver.We recently observed that apolipoprotein A-IV (apoA-IV), a highly abundant apolipoprotein, was among the most upregulated proteins in circulation after six weeks of consuming a high-fat diet in humans.However, the impact of dietary changes in regulating apoA-IV, and the potential effects of apoA-IV on regulation of glucose- and lipid metabolism remain to be fully established.Methods: We investigated the regulation of circulating fasting concentrations of apoA-IV in humans in response to diets enriched in either fat or carbohydrates.

Moreover, to study the whole-body and tissue-specific glucose and lipid metabolic effects of apoA-IV, we administrered apoA-IV recombinant protein to mice and isolated pancreatic islets.Results: We demonstrate that in healthy human individuals high-fat intake increased fasting plasma apoA-IV concentrations by up to 54%, while high-carbohydrate intake suppressed plasma apoA-IV concentrations.In mice, administration of apoA-IV acutely lowered blood glucose levels both in lean and obese mice.Interestingly, this was related to a dual mechanism, involving both inhibition of hepatic glucose production and increased glucose uptake into white and brown adipose tissues.

In addition to an effect on hepatic glucose production, the apoA-IV-induced liver proteome revealed increased capacity for lipoprotein clearance.The effects of apoA-IV in the liver and adipose tissues were concomitant with increased whole-body fatty acid oxidation.Upon glucose stimulation, an improvement in glucose tolerance by apoA-IV administration was related to potentiation of glucose-induced insulin secretion, while apoA-IV inhibited glucagon secretion ex vivo in islets.Conclusions: We find that apoA-IV is potently increased by intake of fat in humans, and that several beneficial metabolic effects, previously associated 2010 chevy malibu exhaust manifold with high fat intake in humans, are mimicked by administration of apoA-IV protein to mice.