Isothermal microcalorimetry measures UCP1-mediated thermogenesis in mature brite adipocytes

Muhammad Hamza Bokhari,Jasper Martin Anton De Jong,Ez-Zoubir Amri,Tore Bengtsson,Robert Csikasz,Alice Åslund,Carina Halleskog,Nathalie Boulet,Irina Shabalina,Eva Casadesús Rendos

doi:10.1038/s42003-021-02639-4

Abstract

The activation of thermogenesis in adipose tissue has emerged as an important target for the development of novel anti-obesity therapies. Using multi-well isothermal microcalorimetry, we have demonstrated that mature murine brown and brite adipocytes produce quantifiable heat upon β3-AR stimulation, independently of any anaerobic mechanisms. Additionally, in brite adipocytes lacking UCP1 protein, β3-AR stimulation still induces heat production, albeit to a much lower extent than in their wildtype counterparts, suggesting that UCP1 is an essential component of adrenergic induced thermogenesis in murine brite adipocytes exvivo. Similarly, we could observe an increase in heat production in human-derived adipocytes (hMADS) upon β-AR stimulation. Collectively, these results establish the use of isothermal microcalorimetry as a sensitive and accurate technique for measuring thermogenic responses in intact mature brite adipocytes from murine and human origin.

Highlights

The activation of thermogenesis in adipose tissue has emerged as an important target for the development of novel anti-obesity therapies
The thermogenic capacity of brown adipose tissue is largely attributed to UCP1, a protein embedded within the mitochondrial membrane, that when activated, results in the dissipation of the electrochemical gradient across the mitochondrial membranes leading to increased substrate oxidation and the production of heat[2]
Calorimetry has been used in the past to measure heat production in isolated brown adipocytes[15,16]

Summary

Introduction

The activation of thermogenesis in adipose tissue has emerged as an important target for the development of novel anti-obesity therapies. We could observe an increase in heat production in human-derived adipocytes (hMADS) upon β-AR stimulation These results establish the use of isothermal microcalorimetry as a sensitive and accurate technique for measuring thermogenic responses in intact mature brite adipocytes from murine and human origin. The thermogenic capacity of brown adipose tissue is largely attributed to UCP1, a protein embedded within the mitochondrial membrane, that when activated, results in the dissipation of the electrochemical gradient across the mitochondrial membranes leading to increased substrate oxidation and the production of heat[2]. There exist other populations of UCP1-containing adipocytes that are molecularly distinct but like brown adipocytes, exhibit thermogenic properties to varying degrees[3,4] These are found within white adipose tissue depots and are termed as brite[4] or beige[5]. These discrepancies become evident in brown adipocytes, where adrenergic stimulation induces cellular respiration in cultured[13] but not mature cells derived from UCP1 KO animals[14]

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Results

Conclusion