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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

Reduced oxidative and respiratory capacity in white adipocyte mitochondria of HFD fed mice can be explained by lower enzymatic equipment of the respiratory chain. (A, B) Protein levels of representative subunits of each of the five OXPHOS complexes determined by immunoblot analysis of isolated mitochondria. MitoProfile® total OXPHOS antibody cocktail is targeted against complex I subunit NDUFB8, complex II-30kDa, complex III-Core protein 2, complex IV subunit I, and complex V alpha subunit. Bands were normalized to the outer membrane protein voltage-dependent anion channel (VDAC). Values of the HFD group are expressed as part of the CD group (=1). Data were analyzed by Two-way repeated measures ANOVA (Bonferroni correction) and presented as means ± SD of 3–4 experiments.*p = 0.05, ** = p < 0.01, *** = p < 0.001. (C) Representative OXPHOS immunoblot of isolated mitochondria from posterior subcutaneous adipocytes.
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fig3: Reduced oxidative and respiratory capacity in white adipocyte mitochondria of HFD fed mice can be explained by lower enzymatic equipment of the respiratory chain. (A, B) Protein levels of representative subunits of each of the five OXPHOS complexes determined by immunoblot analysis of isolated mitochondria. MitoProfile® total OXPHOS antibody cocktail is targeted against complex I subunit NDUFB8, complex II-30kDa, complex III-Core protein 2, complex IV subunit I, and complex V alpha subunit. Bands were normalized to the outer membrane protein voltage-dependent anion channel (VDAC). Values of the HFD group are expressed as part of the CD group (=1). Data were analyzed by Two-way repeated measures ANOVA (Bonferroni correction) and presented as means ± SD of 3–4 experiments.*p = 0.05, ** = p < 0.01, *** = p < 0.001. (C) Representative OXPHOS immunoblot of isolated mitochondria from posterior subcutaneous adipocytes.

Mentions: Lower abundance of respiratory chain complexes has been associated with lower OXPHOS capacity in mitochondria [18]. Thus, we quantified protein amount of representative subunits of each of the five OXPHOS complexes in relation to a surrogate marker of total mitochondrial abundance, the outer membrane channel porin/VDAC. Diet-group comparison revealed a significant reduction of the five enzyme complexes in both posterior subcutaneous (p < 0.001) and epididymal adipocyte mitochondria (p < 0.01) of HFD fed mice (Figure 3). Together, the lower absolute respiration capacity of isolated white adipocyte mitochondria of the HFD group may be explained by a decreased abundance in electron transport chain complexes per mitochondrion.


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)

Reduced oxidative and respiratory capacity in white adipocyte mitochondria of HFD fed mice can be explained by lower enzymatic equipment of the respiratory chain. (A, B) Protein levels of representative subunits of each of the five OXPHOS complexes determined by immunoblot analysis of isolated mitochondria. MitoProfile® total OXPHOS antibody cocktail is targeted against complex I subunit NDUFB8, complex II-30kDa, complex III-Core protein 2, complex IV subunit I, and complex V alpha subunit. Bands were normalized to the outer membrane protein voltage-dependent anion channel (VDAC). Values of the HFD group are expressed as part of the CD group (=1). Data were analyzed by Two-way repeated measures ANOVA (Bonferroni correction) and presented as means ± SD of 3–4 experiments.*p = 0.05, ** = p < 0.01, *** = p < 0.001. (C) Representative OXPHOS immunoblot of isolated mitochondria from posterior subcutaneous adipocytes.
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Related In: Results  -  Collection

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fig3: Reduced oxidative and respiratory capacity in white adipocyte mitochondria of HFD fed mice can be explained by lower enzymatic equipment of the respiratory chain. (A, B) Protein levels of representative subunits of each of the five OXPHOS complexes determined by immunoblot analysis of isolated mitochondria. MitoProfile® total OXPHOS antibody cocktail is targeted against complex I subunit NDUFB8, complex II-30kDa, complex III-Core protein 2, complex IV subunit I, and complex V alpha subunit. Bands were normalized to the outer membrane protein voltage-dependent anion channel (VDAC). Values of the HFD group are expressed as part of the CD group (=1). Data were analyzed by Two-way repeated measures ANOVA (Bonferroni correction) and presented as means ± SD of 3–4 experiments.*p = 0.05, ** = p < 0.01, *** = p < 0.001. (C) Representative OXPHOS immunoblot of isolated mitochondria from posterior subcutaneous adipocytes.
Mentions: Lower abundance of respiratory chain complexes has been associated with lower OXPHOS capacity in mitochondria [18]. Thus, we quantified protein amount of representative subunits of each of the five OXPHOS complexes in relation to a surrogate marker of total mitochondrial abundance, the outer membrane channel porin/VDAC. Diet-group comparison revealed a significant reduction of the five enzyme complexes in both posterior subcutaneous (p < 0.001) and epididymal adipocyte mitochondria (p < 0.01) of HFD fed mice (Figure 3). Together, the lower absolute respiration capacity of isolated white adipocyte mitochondria of the HFD group may be explained by a decreased abundance in electron transport chain complexes per mitochondrion.

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