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 Herrmann, Colleen M. Novak, David Sinclair, James A. Levine, Pinar Aksoy, Eduardo Nunes Chini

Research output: Contribution to journalArticle

99 Citations (Scopus)

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 2007

Fingerprint

NAD+ Nucleosidase
glycosidases
Nutrition
obesity
Obesity
Diet
High Fat Diet
Enzymes
enzymes
diet
Fats
high fat diet
Body Weight
body weight
second messengers
mice
Second Messenger Systems
Organelle Biogenesis
Medical problems
resistance mechanisms

Keywords

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

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. / Barbosa, Maria Thereza P; Herrmann, Sandra; Novak, Colleen M.; Sinclair, David; Levine, James A.; Aksoy, Pinar; Chini, Eduardo Nunes.

In: FASEB Journal, Vol. 21, No. 13, 11.2007, p. 3629-3639.

Research output: Contribution to journalArticle

Barbosa, Maria Thereza P ; Herrmann, Sandra ; Novak, Colleen M. ; Sinclair, David ; Levine, James A. ; Aksoy, Pinar ; Chini, Eduardo Nunes. / The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. In: FASEB Journal. 2007 ; Vol. 21, No. 13. pp. 3629-3639.
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