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At the turn of the 19th century, Ivan Pavlov and others established that the secretion of pancreatic juice is induced upon entry of acidic chyme into the duodenum, and that this pancreatic secretion is accelerated by infusion of hydrochloric acid (HCL) into the stomach. Pavlov hypothesized that secretion of pancreatic juice is induced via a neuronal reflex; however, pancreatic secretion prevailed in dogs following denervation of the intestinal vagal and splanchnic nerves, indicating that pancreatic secretion must be mediated by another, as yet unknown, mechanism.

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

Anne-Marie Lundsgaard, Rita Del Giudice, Josephine M. Kanta, Mark Larance, ... Bente Kiens

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

Objective

Low-carbohydrate, high-fat diets under eucaloric 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 with high fat intake in humans, are mimicked by administration of apoA-IV protein to mice.

Articles in Press

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

Anne-Marie Lundsgaard, Rita Del Giudice, Josephine M. Kanta, Mark Larance, ... Bente Kiens

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

Objective

Low-carbohydrate, high-fat diets under eucaloric 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 with high fat intake in humans, are mimicked by administration of apoA-IV protein to mice.

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12th Helmholtz 
Diabetes Conference 
22-24. Sep, Munich

You are what you eat

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