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

Bioenergetic characterization of isolated mitochondria from posterior subcutaneous and epididymal white adipocytes of mice fed either HFD or CD for 24 weeks: Obesity causes limited oxidative and respiratory capacity. (A) Bioenergetics of isolated white adipocyte mitochondria were measured using three different substrates (complex II linked substrate succinate and complex I linked substrates pyruvate or palmitate). First, respiration was assessed in presence of substrate only (state 4). Phosphorylating state 3 respiration was measured in the presence of ADP and substrate. ATP synthesis was inhibited and state 4o respiration was induced by oligomycin. Addition of the chemical uncoupler FCCP resulted in maximal uncoupled respiration (state 3u). Finally, non-biological background was determined by blockade of electron flow at complex III with antimycin A and subtracted from the other respiratory rates. Data were analyzed by Two-way repeated measures ANOVA (Bonferroni correction). (B) Mitochondrial respiratory control ratio (RCR) was calculated as indicator for mitochondrial integrity. It is defined as the ratio of state 3 to state 4o oxygen consumption (Succ = succinate, Pyr = pyruvate, Mal = malate, PaC = palmitoyl-l-carnitine). Data were analyzed by Student's t-test. Data are presented as means ± SD of 3–4 experiments.*p = 0.05, ** = p < 0.01, *** = p < 0.001.
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fig2: Bioenergetic characterization of isolated mitochondria from posterior subcutaneous and epididymal white adipocytes of mice fed either HFD or CD for 24 weeks: Obesity causes limited oxidative and respiratory capacity. (A) Bioenergetics of isolated white adipocyte mitochondria were measured using three different substrates (complex II linked substrate succinate and complex I linked substrates pyruvate or palmitate). First, respiration was assessed in presence of substrate only (state 4). Phosphorylating state 3 respiration was measured in the presence of ADP and substrate. ATP synthesis was inhibited and state 4o respiration was induced by oligomycin. Addition of the chemical uncoupler FCCP resulted in maximal uncoupled respiration (state 3u). Finally, non-biological background was determined by blockade of electron flow at complex III with antimycin A and subtracted from the other respiratory rates. Data were analyzed by Two-way repeated measures ANOVA (Bonferroni correction). (B) Mitochondrial respiratory control ratio (RCR) was calculated as indicator for mitochondrial integrity. It is defined as the ratio of state 3 to state 4o oxygen consumption (Succ = succinate, Pyr = pyruvate, Mal = malate, PaC = palmitoyl-l-carnitine). Data were analyzed by Student's t-test. Data are presented as means ± SD of 3–4 experiments.*p = 0.05, ** = p < 0.01, *** = p < 0.001.

Mentions: We prepared mitochondria from adipocytes of both fat depots to study organelle respiratory function free of other cellular influences and undisturbed by differences in mitochondrial abundance [4]. Leak respiration (substrate only = state 4, and state 4o) of mitochondria from both fat depots of the HFD group tended to be lower irrespective of the substrate applied (succinate, pyruvate or palmitate), but this diet effect did not reach significance. In contrast, mitochondria from the HFD group consistently stood out by a marked reduction of phosphorylating (state 3) and maximal respiratory capacity (state 3u) (Figure 2A).


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)

Bioenergetic characterization of isolated mitochondria from posterior subcutaneous and epididymal white adipocytes of mice fed either HFD or CD for 24 weeks: Obesity causes limited oxidative and respiratory capacity. (A) Bioenergetics of isolated white adipocyte mitochondria were measured using three different substrates (complex II linked substrate succinate and complex I linked substrates pyruvate or palmitate). First, respiration was assessed in presence of substrate only (state 4). Phosphorylating state 3 respiration was measured in the presence of ADP and substrate. ATP synthesis was inhibited and state 4o respiration was induced by oligomycin. Addition of the chemical uncoupler FCCP resulted in maximal uncoupled respiration (state 3u). Finally, non-biological background was determined by blockade of electron flow at complex III with antimycin A and subtracted from the other respiratory rates. Data were analyzed by Two-way repeated measures ANOVA (Bonferroni correction). (B) Mitochondrial respiratory control ratio (RCR) was calculated as indicator for mitochondrial integrity. It is defined as the ratio of state 3 to state 4o oxygen consumption (Succ = succinate, Pyr = pyruvate, Mal = malate, PaC = palmitoyl-l-carnitine). Data were analyzed by Student's t-test. Data are presented as means ± SD of 3–4 experiments.*p = 0.05, ** = p < 0.01, *** = p < 0.001.
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fig2: Bioenergetic characterization of isolated mitochondria from posterior subcutaneous and epididymal white adipocytes of mice fed either HFD or CD for 24 weeks: Obesity causes limited oxidative and respiratory capacity. (A) Bioenergetics of isolated white adipocyte mitochondria were measured using three different substrates (complex II linked substrate succinate and complex I linked substrates pyruvate or palmitate). First, respiration was assessed in presence of substrate only (state 4). Phosphorylating state 3 respiration was measured in the presence of ADP and substrate. ATP synthesis was inhibited and state 4o respiration was induced by oligomycin. Addition of the chemical uncoupler FCCP resulted in maximal uncoupled respiration (state 3u). Finally, non-biological background was determined by blockade of electron flow at complex III with antimycin A and subtracted from the other respiratory rates. Data were analyzed by Two-way repeated measures ANOVA (Bonferroni correction). (B) Mitochondrial respiratory control ratio (RCR) was calculated as indicator for mitochondrial integrity. It is defined as the ratio of state 3 to state 4o oxygen consumption (Succ = succinate, Pyr = pyruvate, Mal = malate, PaC = palmitoyl-l-carnitine). Data were analyzed by Student's t-test. Data are presented as means ± SD of 3–4 experiments.*p = 0.05, ** = p < 0.01, *** = p < 0.001.
Mentions: We prepared mitochondria from adipocytes of both fat depots to study organelle respiratory function free of other cellular influences and undisturbed by differences in mitochondrial abundance [4]. Leak respiration (substrate only = state 4, and state 4o) of mitochondria from both fat depots of the HFD group tended to be lower irrespective of the substrate applied (succinate, pyruvate or palmitate), but this diet effect did not reach significance. In contrast, mitochondria from the HFD group consistently stood out by a marked reduction of phosphorylating (state 3) and maximal respiratory capacity (state 3u) (Figure 2A).

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