Uncoupling protein-2 modulates the lipid metabolic response to fasting in mice

Anthony R. Sheets, Péter Fülöp, Zoltán Derdák, Andrea Kassai, Edmond Sabo, Nicholas M. Mark, G. Paragh, Jack R. Wands, György Baffy

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Uncoupling protein-2 (UCP2) regulates insulin secretion by controlling ATP levels in β-cells. Although UCP2 deficiency improves glycemic control in mice, increased expression of UCP2 interferes with glucose-stimulated insulin secretion. These observations link UCP2 to β-cell dysfunction in type 2 diabetes with a perplexing evolutionary role. We found higher residual serum insulin levels and blunted lipid metabolic responses in fasted ucp2 -/- mice, supporting the concept that UCP2 evolved to suppress insulin effects and to accommodate the fuel switch to fatty acids during starvation. In the absence of UCP2, fasting initially promotes peripheral lipolysis and hepatic fat accumulation at less than expected rates but culminates in protracted steatosis, indicating diminished hepatic utilization and clearance of fatty acids. We conclude that UCP2-mediated control of insulin secretion is a physiologically relevant mechanism of the metabolic response to fasting.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume294
Issue number4
DOIs
Publication statusPublished - Apr 2008

Fingerprint

Fasting
Lipids
Insulin
Fatty Acids
Protein Deficiency
Lipolysis
Liver
Starvation
Uncoupling Protein 2
Type 2 Diabetes Mellitus
Adenosine Triphosphate
Fats
Glucose
Serum

Keywords

  • Insulin secretion
  • Lipolysis
  • Prolonged fasting
  • Steatosis

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Uncoupling protein-2 modulates the lipid metabolic response to fasting in mice. / Sheets, Anthony R.; Fülöp, Péter; Derdák, Zoltán; Kassai, Andrea; Sabo, Edmond; Mark, Nicholas M.; Paragh, G.; Wands, Jack R.; Baffy, György.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 294, No. 4, 04.2008.

Research output: Contribution to journalArticle

Sheets, Anthony R. ; Fülöp, Péter ; Derdák, Zoltán ; Kassai, Andrea ; Sabo, Edmond ; Mark, Nicholas M. ; Paragh, G. ; Wands, Jack R. ; Baffy, György. / Uncoupling protein-2 modulates the lipid metabolic response to fasting in mice. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2008 ; Vol. 294, No. 4.
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