The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity

Maria Thereza P. Barbosa, Sandra M. Soares, Colleen M. Novak, David Sinclair, James A. Levine, Pinar Aksoy, Eduardo Nunes Chini

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

Obesity is one of the major health problems of our times. Elucidating the signaling mechanisms by which high-fat caloric diet induces obesity is critical for the understanding of this condition and for the development of therapeutic strategies for its treatment. Here, we demonstrate a novel role for protein CD38 as a regulator of body weight during a high-fat diet. CD38 is a ubiquitous enzyme that catalyzes the synthesis of second messengers and has been implicated in the regulation of a wide variety of signaling pathways. We report that CD38-deficient mice are protected against high-fat diet-induced obesity owing to enhanced energy expenditure. In fact, calorimetric studies indicate that CD38-deficient animals have a higher metabolic rate compared to control mice. Analysis of the mechanism revealed that this resistance to diet-induced obesity is mediated at least in part via a NAD-dependent activation of SIRT-PGC1α axis, a wellestablished cascade, involved in the regulation of mitochondrial biogenesis and energy homeostasis. Thus, together these results identify a novel pathway regulating body weight and clearly show that CD38 is a nearly obligatory component of the cellular cascade that led to diet-induced obesity.

Original languageEnglish (US)
Pages (from-to)3629-3639
Number of pages11
JournalFASEB Journal
Volume21
Issue number13
DOIs
StatePublished - Nov 1 2007

Keywords

  • Knockout mice
  • Liver
  • Nicotinamide adenine dinucleotide
  • PGC1α
  • SIRT1
  • Sirtuins

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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