The brown and brite adipocyte marker Cox7a1 is not required for non-shivering thermogenesis in mice

Stefanie F Maurer,Maik Hüttemann,Tobias Fromme,Lawrence I Grossman,Martin Klingenspor

doi:10.1038/srep17704

Stefanie F Maurer, Maik Hüttemann + Show 3 more

Open Access

https://doi.org/10.1038/srep17704

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Abstract

The cytochrome c oxidase subunit isoform Cox7a1 is highly abundant in skeletal muscle and heart and influences enzyme activity in these tissues characterised by high oxidative capacity. We identified Cox7a1, well-known as brown adipocyte marker gene, as a cold-responsive protein of brown adipose tissue. We hypothesised a mechanistic relationship between cytochrome c oxidase activity and Cox7a1 protein levels affecting the oxidative capacity of brown adipose tissue and thus non-shivering thermogenesis. We subjected wildtype and Cox7a1 knockout mice to different temperature regimens and tested characteristics of brown adipose tissue activation. Cytochrome c oxidase activity, uncoupling protein 1 expression and maximal norepinephrine-induced heat production were gradually increased during cold-acclimation, but unaffected by Cox7a1 knockout. Moreover, the abundance of uncoupling protein 1 competent brite cells in white adipose tissue was not influenced by presence or absence of Cox7a1. Skin temperature in the interscapular region of neonates was lower in uncoupling protein 1 knockout pups employed as a positive control, but not in Cox7a1 knockout pups. Body mass gain and glucose tolerance did not differ between wildtype and Cox7a1 knockout mice fed with high fat or control diet. We conclude that brown adipose tissue function in mice does not require the presence of Cox7a1.

Highlights

The cytochrome c oxidase subunit isoform Complex IV subunit 7a isoform 1 (Cox7a1) is highly abundant in skeletal muscle and heart and influences enzyme activity in these tissues characterised by high oxidative capacity
Brown and brite adipocytes are not derived from the same developmental lineage[4], both cell types are first and foremost characterised by a multilocular appearance, high mitochondrial abundance and the expression of mitochondrial uncoupling protein 1 (Ucp1)
Since Brown adipose tissue (BAT) is the major site for adaptive heat production in mammals exposed to low environmental temperatures, we hypothesised that cold-induced upregulation of Cox7a1 in BAT might contribute to that process via modification of cytochrome c oxidase (COX) activity

Summary

Introduction

The cytochrome c oxidase subunit isoform Cox7a1 is highly abundant in skeletal muscle and heart and influences enzyme activity in these tissues characterised by high oxidative capacity. Brown and brite adipocytes are not derived from the same developmental lineage[4], both cell types are first and foremost characterised by a multilocular appearance, high mitochondrial abundance and the expression of mitochondrial uncoupling protein 1 (Ucp[1]). The latter is considered to be the key thermogenic factor mediating NST in BAT depots. To extend the relevance of these molecules from only a marker to a functionally important component, the use of genetically modified mice represents an appropriate strategy This has, by far not been investigated for the majority of candidates that come into question. Cox7a has been described as a late-stage assembly subunit that integrates peripherally into the pre-existing complex and might be involved in the maturation of the final holoenzyme[20]

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