Abstract
The effects of insulin on the bioenergetic and thermogenic capacity of brown adipocyte mitochondria were investigated by focusing on key mitochondrial proteins. Two-month-old male Wistar rats were treated acutely or chronically with a low or high dose of insulin. Acute low insulin dose increased expression of all electron transport chain complexes and complex IV activity, whereas high dose increased complex II expression. Chronic low insulin dose decreased complex I and cyt c expression while increasing complex II and IV expression and complex IV activity. Chronic high insulin dose decreased complex II, III, cyt c, and increased complex IV expression. Uncoupling protein (UCP) 1 expression was decreased after acute high insulin but increased following chronic insulin treatment. ATP synthase expression was increased after acute and decreased after chronic insulin treatment. Only a high dose of insulin increased ATP synthase activity in acute and decreased it in chronic treatment. ATPase inhibitory factor protein expression was increased in all treated groups. Confocal microscopy showed that key mitochondrial proteins colocalize differently in different mitochondria within a single brown adipocyte, indicating mitochondrial mosaicism. These results suggest that insulin modulates the bioenergetic and thermogenic capacity of rat brown adipocytes in vivo by modulating mitochondrial mosaicism.
Highlights
Brown adipose tissue (BAT) is a unique mammalian organ involved in maintaining body temperature and regulating body weight and energy balance through non-shivering thermogenesis [1]
Bearing in mind that the protein expression profile in whole tissue does not represent mitochondria-only proteins, we first decided to examine the effects of hyperinsulinemia on key mitochondrial electron transport chain (ETC) complexes, ATP synthase, and UCP1 protein expression on isolated mitochondria
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Summary
Brown adipose tissue (BAT) is a unique mammalian organ involved in maintaining body temperature and regulating body weight and energy balance through non-shivering thermogenesis [1]. The interplay between thermogenesis, insulin, and BAT mitochondria and their role in diabetes and obesity has been debated for many years since early studies revealed a specific decrease in mitochondrial thermogenic capacity [8] and major thermogenic defects associated with insulin resistance in brown adipose tissue of obese diabetic rats [9]. Brown adipocytes show intracellular mitochondrial heterogeneity, e.g., differences between peridroplet and cytoplasmic mitochondria [14], the exact role of the Harlequin effect remains unclear It is not known whether brown adipocytes exhibit heterogeneous expression of other mitochondrial proteins, especially those involved in bioenergetic capacity. Our previous studies showed that insulin treatment affects BAT mitochondria, were a high chronic dose induced mitochondrial damage and lipofuscin formation [26] as well as apoptosis of brown adipocytes [27], demonstrating the role of insulin in tissue energetic/thermogenic profiling. We attempted to elucidate how insulin modulates the mitochondrial bioenergetic and thermogenic capacity of brown adipocytes by analyzing the expression and colocalization of key mitochondrial proteins, i.e., ETC complexes, ATP synthase, and UCP1
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