Limits...
Limited OXPHOS capacity in white adipocytes is a hallmark of obesity in laboratory mice irrespective of the glucose tolerance status.

Schöttl T, Kappler L, Fromme T, Klingenspor M - Mol Metab (2015)

Bottom Line: Maximal respiration capacity and cell respiratory control ratios were diminished in white adipocytes of each of the four murine obesity models, both in the absence and the presence of impaired glucose tolerance.Limitation was more pronounced in adipocytes of intraabdominal versus subcutaneous fat.Impaired respiratory capacity in white adipocytes solely is not sufficient for the development of systemic glucose intolerance.

View Article: PubMed Central - PubMed

Affiliation: Molecular Nutritional Medicine, Technische Universität München, Else Kröner Fresenius Center for Nutritional Medicine, Freising, Germany.

ABSTRACT

Objective: Several human and rodent obesity studies speculate on a causal link between altered white adipocyte mitochondria in the obese state and changes in glucose homeostasis. We here aimed to dissect whether alterations in white adipocyte mitochondrial respiratory function are a specific phenomenon of obesity or impaired glucose tolerance or both.

Methods: Mature white adipocytes were purified from posterior subcutaneous and intraabdominal epididymal fat of four murine obesity models characterized by either impaired or normal oral glucose tolerance. Bioenergetic profiles, including basal, leak, and maximal respiration, were generated using high-resolution respirometry. Cell respiratory control ratios were calculated to evaluate mitochondrial respiratory function.

Results: Maximal respiration capacity and cell respiratory control ratios were diminished in white adipocytes of each of the four murine obesity models, both in the absence and the presence of impaired glucose tolerance. Limitation was more pronounced in adipocytes of intraabdominal versus subcutaneous fat.

Conclusion: Reduced mitochondrial respiratory capacity in white adipocytes is a hallmark of murine obesity irrespective of the glucose tolerance status. Impaired respiratory capacity in white adipocytes solely is not sufficient for the development of systemic glucose intolerance.

No MeSH data available.


Related in: MedlinePlus

Cellular respiration of adipocytes from HF-recovery and CD mice. Recovery intervention does not restore limited maximal respiratory capacity and reduced mitochondrial integrity. (A, B) First, basal respiration was assessed using pyruvate as a substrate. ATP synthase inhibitor oligomycin was added to define the proportion of basal respiration contributing to either ATP turnover or proton leak, respectively. Next, FCCP was added to determine the maximal cellular respiratory capacity. Lastly, non-mitochondrial background was determined by addition of complex III inhibitor antimycin A and subtracted from the other respiratory states. Oxygen consumption rates are expressed per μg DNA. (C, D) Spare respiratory capacity = max – basal. (E, F) Citrate synthase activity was measured as marker for mitochondrial abundance and expressed as CS activity per μg DNA. (G, H) Cell respiratory control ratio (cRCR) was calculated as an index for mitochondrial integrity (quotient of maximal to leak oxygen consumption). A-B was analyzed by Two-way repeated measures ANOVA (Bonferroni correction. C-H was analyzed by Student's t-test. Data are presented as means ± SD of 5–7 experiments. p < 0.05, ** = p < 0.01, *** = p < 0.001.
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fig7: Cellular respiration of adipocytes from HF-recovery and CD mice. Recovery intervention does not restore limited maximal respiratory capacity and reduced mitochondrial integrity. (A, B) First, basal respiration was assessed using pyruvate as a substrate. ATP synthase inhibitor oligomycin was added to define the proportion of basal respiration contributing to either ATP turnover or proton leak, respectively. Next, FCCP was added to determine the maximal cellular respiratory capacity. Lastly, non-mitochondrial background was determined by addition of complex III inhibitor antimycin A and subtracted from the other respiratory states. Oxygen consumption rates are expressed per μg DNA. (C, D) Spare respiratory capacity = max – basal. (E, F) Citrate synthase activity was measured as marker for mitochondrial abundance and expressed as CS activity per μg DNA. (G, H) Cell respiratory control ratio (cRCR) was calculated as an index for mitochondrial integrity (quotient of maximal to leak oxygen consumption). A-B was analyzed by Two-way repeated measures ANOVA (Bonferroni correction. C-H was analyzed by Student's t-test. Data are presented as means ± SD of 5–7 experiments. p < 0.05, ** = p < 0.01, *** = p < 0.001.

Mentions: Respirometry of intact adipocytes revealed no difference between the CD und the HF-recovery group in basal and leak respiration. Maximal oxygen consumption of both types of adipocytes, however, was lower in the HF-recovery group (Figure 7A,B). Concordantly, spare respiratory capacity was reduced in adipocytes of HF-recovery mice (Figure 7C,D). Thus, adipocytes of HF-recovery mice displayed a lower ability to increase substrate oxidation compared to CD mice. Mitochondrial abundance, based on CS activity per cell, was reduced in adipocytes of HF-recovery mice (Figure 7E,F). Cellular RCR was comparable in posterior subcutaneous but markedly decreased in epididymal adipocytes (Figure 7G,H). Thus, limited maximal cellular respiration in epididymal adipocytes is clearly ascribable to both lower mitochondrial abundance and lower mitochondrial capacity. In posterior subcutaneous adipocytes, mitochondrial abundance alone explains the diminished cellular respiratory capacity.


Limited OXPHOS capacity in white adipocytes is a hallmark of obesity in laboratory mice irrespective of the glucose tolerance status.

Schöttl T, Kappler L, Fromme T, Klingenspor M - Mol Metab (2015)

Cellular respiration of adipocytes from HF-recovery and CD mice. Recovery intervention does not restore limited maximal respiratory capacity and reduced mitochondrial integrity. (A, B) First, basal respiration was assessed using pyruvate as a substrate. ATP synthase inhibitor oligomycin was added to define the proportion of basal respiration contributing to either ATP turnover or proton leak, respectively. Next, FCCP was added to determine the maximal cellular respiratory capacity. Lastly, non-mitochondrial background was determined by addition of complex III inhibitor antimycin A and subtracted from the other respiratory states. Oxygen consumption rates are expressed per μg DNA. (C, D) Spare respiratory capacity = max – basal. (E, F) Citrate synthase activity was measured as marker for mitochondrial abundance and expressed as CS activity per μg DNA. (G, H) Cell respiratory control ratio (cRCR) was calculated as an index for mitochondrial integrity (quotient of maximal to leak oxygen consumption). A-B was analyzed by Two-way repeated measures ANOVA (Bonferroni correction. C-H was analyzed by Student's t-test. Data are presented as means ± SD of 5–7 experiments. p < 0.05, ** = p < 0.01, *** = p < 0.001.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
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fig7: Cellular respiration of adipocytes from HF-recovery and CD mice. Recovery intervention does not restore limited maximal respiratory capacity and reduced mitochondrial integrity. (A, B) First, basal respiration was assessed using pyruvate as a substrate. ATP synthase inhibitor oligomycin was added to define the proportion of basal respiration contributing to either ATP turnover or proton leak, respectively. Next, FCCP was added to determine the maximal cellular respiratory capacity. Lastly, non-mitochondrial background was determined by addition of complex III inhibitor antimycin A and subtracted from the other respiratory states. Oxygen consumption rates are expressed per μg DNA. (C, D) Spare respiratory capacity = max – basal. (E, F) Citrate synthase activity was measured as marker for mitochondrial abundance and expressed as CS activity per μg DNA. (G, H) Cell respiratory control ratio (cRCR) was calculated as an index for mitochondrial integrity (quotient of maximal to leak oxygen consumption). A-B was analyzed by Two-way repeated measures ANOVA (Bonferroni correction. C-H was analyzed by Student's t-test. Data are presented as means ± SD of 5–7 experiments. p < 0.05, ** = p < 0.01, *** = p < 0.001.
Mentions: Respirometry of intact adipocytes revealed no difference between the CD und the HF-recovery group in basal and leak respiration. Maximal oxygen consumption of both types of adipocytes, however, was lower in the HF-recovery group (Figure 7A,B). Concordantly, spare respiratory capacity was reduced in adipocytes of HF-recovery mice (Figure 7C,D). Thus, adipocytes of HF-recovery mice displayed a lower ability to increase substrate oxidation compared to CD mice. Mitochondrial abundance, based on CS activity per cell, was reduced in adipocytes of HF-recovery mice (Figure 7E,F). Cellular RCR was comparable in posterior subcutaneous but markedly decreased in epididymal adipocytes (Figure 7G,H). Thus, limited maximal cellular respiration in epididymal adipocytes is clearly ascribable to both lower mitochondrial abundance and lower mitochondrial capacity. In posterior subcutaneous adipocytes, mitochondrial abundance alone explains the diminished cellular respiratory capacity.

Bottom Line: Maximal respiration capacity and cell respiratory control ratios were diminished in white adipocytes of each of the four murine obesity models, both in the absence and the presence of impaired glucose tolerance.Limitation was more pronounced in adipocytes of intraabdominal versus subcutaneous fat.Impaired respiratory capacity in white adipocytes solely is not sufficient for the development of systemic glucose intolerance.

View Article: PubMed Central - PubMed

Affiliation: Molecular Nutritional Medicine, Technische Universität München, Else Kröner Fresenius Center for Nutritional Medicine, Freising, Germany.

ABSTRACT

Objective: Several human and rodent obesity studies speculate on a causal link between altered white adipocyte mitochondria in the obese state and changes in glucose homeostasis. We here aimed to dissect whether alterations in white adipocyte mitochondrial respiratory function are a specific phenomenon of obesity or impaired glucose tolerance or both.

Methods: Mature white adipocytes were purified from posterior subcutaneous and intraabdominal epididymal fat of four murine obesity models characterized by either impaired or normal oral glucose tolerance. Bioenergetic profiles, including basal, leak, and maximal respiration, were generated using high-resolution respirometry. Cell respiratory control ratios were calculated to evaluate mitochondrial respiratory function.

Results: Maximal respiration capacity and cell respiratory control ratios were diminished in white adipocytes of each of the four murine obesity models, both in the absence and the presence of impaired glucose tolerance. Limitation was more pronounced in adipocytes of intraabdominal versus subcutaneous fat.

Conclusion: Reduced mitochondrial respiratory capacity in white adipocytes is a hallmark of murine obesity irrespective of the glucose tolerance status. Impaired respiratory capacity in white adipocytes solely is not sufficient for the development of systemic glucose intolerance.

No MeSH data available.


Related in: MedlinePlus