Role of adiponectin in the metabolic effects of cannabinoid type 1 receptor blockade in mice with diet-induced obesity

Joseph Tam, Grzegorz Godlewski, Brian J. Earley, Liang Zhou, Tony Jourdan, G. Szanda, Resat Cinar, George Kunos

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The adipocyte-derived hormone adiponectin promotes fatty acid oxidation and improves insulin sensitivity and thus plays a key role in the regulation of lipid and glucose metabolism and energy homeostasis. Chronic cannabinoid type 1 (CB1) receptor blockade also increases lipid oxidation and improves insulin sensitivity in obese individuals or animals, resulting in reduced cardiometabolic risk. Chronic CB1 blockade reverses the obesity-related decline in serum adiponectin levels, which has been proposed to account for the metabolic effects of CB1 antagonists. Here, we investigated the metabolic actions of the CB1 inverse agonist rimonabant in high-fat diet (HFD)-induced obese adiponectin knockout (Adipo-/-) mice and their wild-type littermate controls (Adipo+/+). HFD-induced obesity and its hormonal/metabolic consequences were indistinguishable in the two strains. Daily treatment of obese mice with rimonabant for 7 days resulted in significant and comparable reductions in body weight, serum leptin, free fatty acid, cholesterol, and triglyceride levels in the two strains. Rimonabant treatment improved glucose homeostasis and insulin sensitivity to the same extent in Adipo+/+ and Adipo-/- mice, whereas it reversed the HFD-induced hepatic steatosis, fibrosis, and hepatocellular damage only in the former. The adiponectin-dependent, antisteatotic effect of rimonabant was mediated by reduced uptake and increased β-oxidation of fatty acids in the liver. We conclude that reversal of the HFD-induced hepatic steatosis and fibrosis by chronic CB1 blockade, but not the parallel reduction in adiposity and improved glycemic control, is mediated by adiponectin.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume306
Issue number4
DOIs
Publication statusPublished - Feb 15 2014

Fingerprint

rimonabant
Cannabinoid Receptors
Adiponectin
High Fat Diet
Obesity
Cannabinoids
Diet
Insulin Resistance
Liver
Homeostasis
Fibrosis
Fatty Acids
Cannabinoid Receptor Antagonists
Glucose
Obese Mice
Adiposity
Leptin
Serum
Lipid Metabolism
Nonesterified Fatty Acids

Keywords

  • Cannabinoid type 1 antagonism
  • Fatty acid uptake
  • Hepatic steatosis and fibrosis
  • Insulin resistance

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Role of adiponectin in the metabolic effects of cannabinoid type 1 receptor blockade in mice with diet-induced obesity. / Tam, Joseph; Godlewski, Grzegorz; Earley, Brian J.; Zhou, Liang; Jourdan, Tony; Szanda, G.; Cinar, Resat; Kunos, George.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 306, No. 4, 15.02.2014.

Research output: Contribution to journalArticle

Tam, Joseph ; Godlewski, Grzegorz ; Earley, Brian J. ; Zhou, Liang ; Jourdan, Tony ; Szanda, G. ; Cinar, Resat ; Kunos, George. / Role of adiponectin in the metabolic effects of cannabinoid type 1 receptor blockade in mice with diet-induced obesity. In: American Journal of Physiology - Endocrinology and Metabolism. 2014 ; Vol. 306, No. 4.
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