Acute induction of uncoupling protein 1 by citrulline in cultured explants of white adipose tissue from lean and high-fat-diet-fed rats

Abstract

A diet enriched with citrulline (CIT) reduces white adipose tissue (WAT) mass. We recently showed that CIT stimulated β-oxidation in rat WAT explants from young (2–4 months) but not old (25 months) rats. Here we show that both in old rats and high-fat-diet-fed young rats, uncoupling protein one (UCP1) mRNA and protein expressions were weaker than those in young control rats. Selectively in WAT from young rats, a 24h CIT treatment up-regulated expressions of UCP1, peroxisome proliferator-activated receptor-α (PPARα), PPARγ-coactivator-1-α and mitochondrial-transcription-factor-A whereas it down-regulated PPARγ2 gene expression, whatever the diet. These results suggest that CIT induces a new metabolic status in WAT, with increased β-oxidation and uncoupling of respiratory chain, resulting in energy expenditure that favors fat mass reduction.

Keywords:

• adipose tissue
• browning
• citrulline
• fatty acids
• obesity
• UCP1

Abbreviations:

• ARG, arginine
• ASL, argininosuccinate lyase
• ASS, argininosuccinate synthase
• BSA, bovine serum albumin
• CD, control diet
• CIT, citrulline
• CPT1-b, carnitine palmitoyl transferase 1-b
• EPI, epididymal
• HFD, high-fat-diet
• KREBS, Krebs Ringer Buffer Saline
• NEFA, non-esterified fatty acids
• NO, nitric oxide
• NOS, nitric oxide synthase
• PEPCK-C, cytosolic phosphoenolpyruvate carboxykinase
• PGC-1α, peroxisome proliferator-activated receptor gamma co-activator 1α
• PKA, protein kinase A
• PPAR, peroxisome proliferator-activated receptor
• RET, retroperitoneal
• TFAM, mitochondrial transcription factor A
• VLCAD, very long chain acyl-CoA dehydrogenase
• WAT, white adipose tissue

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgment

We thank Dr. Brigitte Potier for providing us with a series of old rats.

Funding

We acknowledge the Institut National de la Santé et de la Recherche Médicale and the Université Paris Descartes for their financial support.