Abstract

The recent characterization of functional brown adipose tissue in adult humans has opened new perspectives for regulation of energy expenditure with respect to obesity and diabetes. Furthermore, dietary recommendations have taken into account the insufficient dietary intake of ω3 PUFAs and the concomitant excessive intake of ω6 PUFA associated with the occurrence of overweight/obesity. We aimed to study whether ω3 PUFAs could play a role in the recruitment and function of energy-dissipating brown/brite adipocytes. We show that ω3 PUFA supplementation has a beneficial effect on the thermogenic function of adipocytes. In vivo, a low dietary ω6:ω3 ratio improved the thermogenic response of brown and white adipose tissues to β3-adrenergic stimulation. This effect was recapitulated in vitro by PUFA treatment of hMADS adipocytes. We pinpointed the ω6-derived eicosanoid prostaglandin (PG)F2α as the molecular origin because the effects were mimicked with a specific PGF2α receptor agonist. PGF2α level in hMADS adipocytes was reduced in response to ω3 PUFA supplementation. The recruitment of thermogenic adipocytes is influenced by the local quantity of individual oxylipins, which is controlled by the ω6:ω3 ratio of available lipids. In human nutrition, energy homeostasis may thus benefit from the implementation of a more balanced dietary ω6:ω3 ratio.

Highlights

  • The recent characterization of functional brown adipose tissue in adult humans has opened new perspectives for regulation of energy expenditure with respect to obesity and diabetes

  • 3 diet-fed mice showed a larger decrease in body mass and adipose tissue mass on CL316,243-treatment compared with 6 diet-fed mice (Fig. 1A,B)

  • Previous studies demonstrated the 6 eicosanoid prostacyclin (PGI2, which is derived from arachidonic acid (ARA) via COX-dependent metabolization) as a positive modulator of uncoupling protein 1 (UCP1) expression and brite adipogenesis in human and murine cellular model systems [42, 45,46,47]

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Summary

Introduction

The recent characterization of functional brown adipose tissue in adult humans has opened new perspectives for regulation of energy expenditure with respect to obesity and diabetes. We aimed to study whether 3 PUFAs could play a role in the recruitment and function of energy-dissipating brown/brite adipocytes. We show that 3 PUFA supplementation has a beneficial effect on the thermogenic function of adipocytes. A low dietary 6: 3 ratio improved the thermogenic response of brown and white adipose tissues to 3-adrenergic stimulation. This effect was recapitulated in vitro by PUFA treatment of hMADS adipocytes. Impact of dietary 3 polyunsaturated fatty acid supplementation on brown and brite adipocyte function J.

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