Dataset Information

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

ABSTRACT: 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 the circulation after six weeks of high fat intake in humans. However, the dietary regulation of apoA-IV and the potential effects of apoA-IV on regulation of glucose- and lipid metabolism remain to be fully established. We here demonstrate in healthy human individuals that both short- and long-term 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 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 obtained 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. In conclusion, we find that ApoA-IV is potently increased by the 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Mark Larance

LAB HEAD: Mark Larance

PROVIDER: PXD055918 | Pride | 2025-05-07

REPOSITORIES: Pride

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			Action	DRS
	20190808_Lumos_DH_EXP161_ApoA4_Liver_1.raw	Raw
	20190808_Lumos_DH_EXP161_ApoA4_Liver_10.raw	Raw
	20190808_Lumos_DH_EXP161_ApoA4_Liver_11.raw	Raw
	20190808_Lumos_DH_EXP161_ApoA4_Liver_12.raw	Raw
	20190808_Lumos_DH_EXP161_ApoA4_Liver_13.raw	Raw

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

Lundsgaard Anne-Marie AM Del Giudice Rita R Kanta Josephine M JM Larance Mark M Armour Sarah L SL London Amalie A Richter Michael M MM Andersen Nicoline R NR Nicolaisen Trine S TS Carl Christian S CS Sjøberg Kim A KA Bojsen-Møller Kirstine Nyvold KN Knudsen Jakob G JG Lagerstedt Jens O JO Fritzen Andreas M AM Kiens Bente B

Molecular metabolism 20250301

<h4>Objective</h4>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 gl ...[more]

PMID: 40032158

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