Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB185

Poster Communications

Limited oxidative phosphorylation capacity in white adipocytes is a hallmark of obesity - irrespective of the glucose tolerance status

T. Schöttl1, T. Fromme1, F. Pachl2, B. Kuster2, M. Klingenspor1

1. Chair of Molecular Nutritional Medicine, Else Kröner Fresenius Center for Nutritional Medicine, Technical University Munich, Freising-Weihenstephan, Germany. 2. Chair of Proteomics and Bioanalytics, Technical University Munich, Freising-Weihenstephan, Germany.


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A series of obesity studies speculate on a causal link between altered mitochondrial metabolism in white adipose tissue and the development of obesity related glucose intolerance. We here aimed i) to define the level of impairment in white adipocyte mitochondria in obesity ii) to clarify the relation between white adipocyte mitochondrial impaired function, obesity, and glucose intolerance. Mice were fed for 6 months a high-fat diet (HFD). We applied a non-targeted proteomic approach to identify the most vulnerable aspect of mitochondrial physiology in this model of obesity and glucose intolerance. Primarily, we found massive reduction in oxidative phosphorylation (OXPHOS) enzymatic equipment, with 40 out of a total of 98 respiratory chain complex subunits significantly downregulated in HFD compared to control mice (n=3, students t-test followed by Benjamini-Hochberg correction, significance level p<0.05). Next, we assessed OXPHOS in white adipocytes on the functional level. We generated bioenergetic profiles comprising basal, leak and maximal respiration, and calculated cellular respiratory control ratios (maximal / leak). In line with the reduction in OXPHOS enzymes, respiratory control ratios were significantly decreased in white adipocytes from HFD fed mice (table 1) (1). Finally, we investigated white adipocyte mitochondrial bioenergetics in three further murine models of obesity (table 1), characterized by either impaired (Lepob/ob) or normal oral glucose tolerance (Mc4RX16/X16, and mice fed one week control diet subsequent to 6 months HFD). Compared to the 6-months HFD feeding model, we found similar reduction in OXPHOS capacity, most notably both in the absence and the presence of impaired glucose tolerance (table 1) (1). Altogether, we here describe systematic downregulation of OXPHOS capacity, due to reduction in enzymatic equipment of the respiratory chain, as a consequence of obesity. Decreased mitochondrial respiratory capacity in white adipocytes proved a hallmark of obesity, irrespective of glucose tolerance status. Thus, impaired OXPHOS capacity in white adipocytes alone is not the proximate trigger for the development of systemic glucose intolerance.

Where applicable, experiments conform with Society ethical requirements