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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

One week refeeding CD following 24 weeks HFD (HF-recovery) is sufficient to restore glucose tolerance. At the age of eight weeks, mice were matched by body weight into HFD and CD groups. The respective diet was fed for 24 weeks then HFD fed mice received CD for one week. (A) Body weight, (B) Fat mass, (C) Lean mass, (D) Oral glucose tolerance test, (E) Total area-under-the-curve (AUC) calculated from D as measure for glucose tolerance. Values of the HF-recovery group are shown both before and after one week CD refeeding. A-E were analyzed by one-way ANOVA. D was analyzed by two way repeated measures ANOVA, * corresponds to comparison between CD and HFD, ° corresponds to comparison between CD and HF-recovery, # corresponds to comparison between HFD and HF-recovery, n = 7, */#/° = p < 0.05, **/##/°° = p < 0.01, ***/###/°°° = p < 0.001.
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fig6: One week refeeding CD following 24 weeks HFD (HF-recovery) is sufficient to restore glucose tolerance. At the age of eight weeks, mice were matched by body weight into HFD and CD groups. The respective diet was fed for 24 weeks then HFD fed mice received CD for one week. (A) Body weight, (B) Fat mass, (C) Lean mass, (D) Oral glucose tolerance test, (E) Total area-under-the-curve (AUC) calculated from D as measure for glucose tolerance. Values of the HF-recovery group are shown both before and after one week CD refeeding. A-E were analyzed by one-way ANOVA. D was analyzed by two way repeated measures ANOVA, * corresponds to comparison between CD and HFD, ° corresponds to comparison between CD and HF-recovery, # corresponds to comparison between HFD and HF-recovery, n = 7, */#/° = p < 0.05, **/##/°° = p < 0.01, ***/###/°°° = p < 0.001.

Mentions: In a previous study, we found glucose tolerance of HFD fed mice to recover shortly after HFD is replaced by CD [23]. In detail, glucose tolerance of 12 weeks HFD fed mice of the strains AKR/J, SWR/J, and C57BL/6J was normalized after one week of CD refeeding. Of note, this phenomenon clearly occurred well in advance of a major decline in diet-induced body fat mass (unpublished data). This model should allow the dissection of a possible causality between white adipocyte mitochondrial function and glucose (in-)tolerance. Thus, we transferred the experimental design of our previous work to the present study and, in a second trial, refed mice with CD for one week after 24 weeks of HFD feeding (HF-recovery). During this period, HF-recovery mice markedly lost weight (HF-recovery −5.081 g ± 1.823 g vs. CD -0.064 g ± 1.640 g, n = 7, p < 0.001) but were still obese as indicated by final body weight and fat mass higher than that of controls (Figure 6A–B). Lean mass was comparable between the feeding groups (Figure 6C). Posterior subcutaneous and epididymal fat pads were significantly larger in HF-recovery compared to control mice, reflecting their contribution to whole body adiposity (posterior subcutaneous: HF-recovery 2.085 g ± 0.376 g vs. CD 0.732 g ± 0.280 g; epididymal: HF-recovery 1.540 g ± 0.156 g vs. CD 0.824 g ± 0.230 g, both n = 7, p < 0.001). Notably, HF-recovery mice displayed improved glucose tolerance which tended to be even better than that of controls (Figure 6D,E). To assess whether compensatory hyperinsulinemia masks peripheral insulin resistance, we analyzed plasma insulin levels. Compared to HFD fed mice HF-recovery mice stood out by significantly lower insulin concentrations which were similar to those of the control group (Table 1).


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)

One week refeeding CD following 24 weeks HFD (HF-recovery) is sufficient to restore glucose tolerance. At the age of eight weeks, mice were matched by body weight into HFD and CD groups. The respective diet was fed for 24 weeks then HFD fed mice received CD for one week. (A) Body weight, (B) Fat mass, (C) Lean mass, (D) Oral glucose tolerance test, (E) Total area-under-the-curve (AUC) calculated from D as measure for glucose tolerance. Values of the HF-recovery group are shown both before and after one week CD refeeding. A-E were analyzed by one-way ANOVA. D was analyzed by two way repeated measures ANOVA, * corresponds to comparison between CD and HFD, ° corresponds to comparison between CD and HF-recovery, # corresponds to comparison between HFD and HF-recovery, n = 7, */#/° = p < 0.05, **/##/°° = p < 0.01, ***/###/°°° = p < 0.001.
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fig6: One week refeeding CD following 24 weeks HFD (HF-recovery) is sufficient to restore glucose tolerance. At the age of eight weeks, mice were matched by body weight into HFD and CD groups. The respective diet was fed for 24 weeks then HFD fed mice received CD for one week. (A) Body weight, (B) Fat mass, (C) Lean mass, (D) Oral glucose tolerance test, (E) Total area-under-the-curve (AUC) calculated from D as measure for glucose tolerance. Values of the HF-recovery group are shown both before and after one week CD refeeding. A-E were analyzed by one-way ANOVA. D was analyzed by two way repeated measures ANOVA, * corresponds to comparison between CD and HFD, ° corresponds to comparison between CD and HF-recovery, # corresponds to comparison between HFD and HF-recovery, n = 7, */#/° = p < 0.05, **/##/°° = p < 0.01, ***/###/°°° = p < 0.001.
Mentions: In a previous study, we found glucose tolerance of HFD fed mice to recover shortly after HFD is replaced by CD [23]. In detail, glucose tolerance of 12 weeks HFD fed mice of the strains AKR/J, SWR/J, and C57BL/6J was normalized after one week of CD refeeding. Of note, this phenomenon clearly occurred well in advance of a major decline in diet-induced body fat mass (unpublished data). This model should allow the dissection of a possible causality between white adipocyte mitochondrial function and glucose (in-)tolerance. Thus, we transferred the experimental design of our previous work to the present study and, in a second trial, refed mice with CD for one week after 24 weeks of HFD feeding (HF-recovery). During this period, HF-recovery mice markedly lost weight (HF-recovery −5.081 g ± 1.823 g vs. CD -0.064 g ± 1.640 g, n = 7, p < 0.001) but were still obese as indicated by final body weight and fat mass higher than that of controls (Figure 6A–B). Lean mass was comparable between the feeding groups (Figure 6C). Posterior subcutaneous and epididymal fat pads were significantly larger in HF-recovery compared to control mice, reflecting their contribution to whole body adiposity (posterior subcutaneous: HF-recovery 2.085 g ± 0.376 g vs. CD 0.732 g ± 0.280 g; epididymal: HF-recovery 1.540 g ± 0.156 g vs. CD 0.824 g ± 0.230 g, both n = 7, p < 0.001). Notably, HF-recovery mice displayed improved glucose tolerance which tended to be even better than that of controls (Figure 6D,E). To assess whether compensatory hyperinsulinemia masks peripheral insulin resistance, we analyzed plasma insulin levels. Compared to HFD fed mice HF-recovery mice stood out by significantly lower insulin concentrations which were similar to those of the control group (Table 1).

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