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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

H2O2release of isolated mitochondria from adipocytes of 24 weeks HFD versus CD fed mice. H2O2 release was assessed in pyruvate or palmitate energized mitochondria using Amplex® Red fluorescence. Measurements were conducted during state 4 (substrate only) and state 3 (substrate + ADP) respiration. Data are presented as means ± SD of 4 experiments. * = p < 0.05.
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fig4: H2O2release of isolated mitochondria from adipocytes of 24 weeks HFD versus CD fed mice. H2O2 release was assessed in pyruvate or palmitate energized mitochondria using Amplex® Red fluorescence. Measurements were conducted during state 4 (substrate only) and state 3 (substrate + ADP) respiration. Data are presented as means ± SD of 4 experiments. * = p < 0.05.

Mentions: Elevated levels of reactive oxygen species (ROS) in adipocytes have been associated with obesity dependent impaired glucose tolerance and insulin resistance [19]. We determined whether mitochondria from posterior subcutaneous and epididymal adipocytes of HFD vs. control diet (CD) fed mice differ in terms of H2O2 efflux, as a result of superoxide radical anion formation. Superoxide, the main ROS produced by the electron transport chain, is converted by superoxide dismutase 2 (SOD2) to membrane permeable H2O2[20,21] which is either released from the mitochondria or degraded by matrix antioxidant processes [22]. Mitochondrial H2O2 efflux, as a surrogate measure for ROS metabolism, was comparable in the two feeding groups of this study. We found no evidence for elevated ROS release from isolated white adipocyte mitochondria, which could be associated with impaired glucose tolerance observed in HFD fed mice. If anything, we detected a minor reduction of ROS release in mitochondria of the HFD group (Figure 4). This finding does not support the view that excessive mitochondrial ROS release in adipocytes from HFD fed mice contributes to the development of impaired glucose metabolism.


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)

H2O2release of isolated mitochondria from adipocytes of 24 weeks HFD versus CD fed mice. H2O2 release was assessed in pyruvate or palmitate energized mitochondria using Amplex® Red fluorescence. Measurements were conducted during state 4 (substrate only) and state 3 (substrate + ADP) respiration. Data are presented as means ± SD of 4 experiments. * = p < 0.05.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563017&req=5

fig4: H2O2release of isolated mitochondria from adipocytes of 24 weeks HFD versus CD fed mice. H2O2 release was assessed in pyruvate or palmitate energized mitochondria using Amplex® Red fluorescence. Measurements were conducted during state 4 (substrate only) and state 3 (substrate + ADP) respiration. Data are presented as means ± SD of 4 experiments. * = p < 0.05.
Mentions: Elevated levels of reactive oxygen species (ROS) in adipocytes have been associated with obesity dependent impaired glucose tolerance and insulin resistance [19]. We determined whether mitochondria from posterior subcutaneous and epididymal adipocytes of HFD vs. control diet (CD) fed mice differ in terms of H2O2 efflux, as a result of superoxide radical anion formation. Superoxide, the main ROS produced by the electron transport chain, is converted by superoxide dismutase 2 (SOD2) to membrane permeable H2O2[20,21] which is either released from the mitochondria or degraded by matrix antioxidant processes [22]. Mitochondrial H2O2 efflux, as a surrogate measure for ROS metabolism, was comparable in the two feeding groups of this study. We found no evidence for elevated ROS release from isolated white adipocyte mitochondria, which could be associated with impaired glucose tolerance observed in HFD fed mice. If anything, we detected a minor reduction of ROS release in mitochondria of the HFD group (Figure 4). This finding does not support the view that excessive mitochondrial ROS release in adipocytes from HFD fed mice contributes to the development of impaired glucose metabolism.

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