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

24 weeks HFD feeding causes massive obesity and impaired glucose tolerance. At the age of eight weeks, mice were matched by body weight into HFD and CD groups. Diets were fed for 24 weeks. All parameters were measured at the end of the feeding period. (A) Body weight (n = 38–41), (B) Fat mass (n = 7), (C) Lean mass (n = 7), (D) Oral glucose tolerance test (n = 7), (E) Total area-under-the-curve (AUC) calculated from D as measure for glucose tolerance (n = 7). A, B, C, E was analyzed by Student's t-test. D was analyzed by two way repeated measures ANOVA. Data are presented as means ± SD. * = p < 0.05, ** = p < 0.01, *** = p < 0.001.
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fig1: 24 weeks HFD feeding causes massive obesity and impaired glucose tolerance. At the age of eight weeks, mice were matched by body weight into HFD and CD groups. Diets were fed for 24 weeks. All parameters were measured at the end of the feeding period. (A) Body weight (n = 38–41), (B) Fat mass (n = 7), (C) Lean mass (n = 7), (D) Oral glucose tolerance test (n = 7), (E) Total area-under-the-curve (AUC) calculated from D as measure for glucose tolerance (n = 7). A, B, C, E was analyzed by Student's t-test. D was analyzed by two way repeated measures ANOVA. Data are presented as means ± SD. * = p < 0.05, ** = p < 0.01, *** = p < 0.001.

Mentions: As a first step, we determined glucose tolerance and white adipocyte mitochondrial OXPHOS functionality in subcutaneous and intraabdominal fat of diet-induced obese mice. At the end of a 24 weeks feeding period, high-fat diet (HFD) fed mice were massively obese as indicated by a higher body and fat mass at a comparable lean mass (Figure 1A–C). Posterior subcutaneous and intraabdominal epididymal fat depots were significantly larger in HFD vs. CD fed mice, reflecting their contribution to whole body adiposity (posterior subcutaneous: HFD 2.836 g ± 0.636 g vs. CD 0.704 g ± 0.255 g; epididymal: HFD 1.714 g ± 0.441 g vs. CD 0.710 g ± 0.311 g, both n = 38–41, p < 0.001). Diet-induced obesity was accompanied by hyperinsulinemia and impaired oral glucose tolerance, reflected by lower glucose clearance and higher area under the curve (AUC, Table 1, Figure 1D,E).


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)

24 weeks HFD feeding causes massive obesity and impaired glucose tolerance. At the age of eight weeks, mice were matched by body weight into HFD and CD groups. Diets were fed for 24 weeks. All parameters were measured at the end of the feeding period. (A) Body weight (n = 38–41), (B) Fat mass (n = 7), (C) Lean mass (n = 7), (D) Oral glucose tolerance test (n = 7), (E) Total area-under-the-curve (AUC) calculated from D as measure for glucose tolerance (n = 7). A, B, C, E was analyzed by Student's t-test. D was analyzed by two way repeated measures ANOVA. Data are presented as means ± SD. * = p < 0.05, ** = p < 0.01, *** = p < 0.001.
© Copyright Policy - CC BY-NC-ND
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getmorefigures.php?uid=PMC4563017&req=5

fig1: 24 weeks HFD feeding causes massive obesity and impaired glucose tolerance. At the age of eight weeks, mice were matched by body weight into HFD and CD groups. Diets were fed for 24 weeks. All parameters were measured at the end of the feeding period. (A) Body weight (n = 38–41), (B) Fat mass (n = 7), (C) Lean mass (n = 7), (D) Oral glucose tolerance test (n = 7), (E) Total area-under-the-curve (AUC) calculated from D as measure for glucose tolerance (n = 7). A, B, C, E was analyzed by Student's t-test. D was analyzed by two way repeated measures ANOVA. Data are presented as means ± SD. * = p < 0.05, ** = p < 0.01, *** = p < 0.001.
Mentions: As a first step, we determined glucose tolerance and white adipocyte mitochondrial OXPHOS functionality in subcutaneous and intraabdominal fat of diet-induced obese mice. At the end of a 24 weeks feeding period, high-fat diet (HFD) fed mice were massively obese as indicated by a higher body and fat mass at a comparable lean mass (Figure 1A–C). Posterior subcutaneous and intraabdominal epididymal fat depots were significantly larger in HFD vs. CD fed mice, reflecting their contribution to whole body adiposity (posterior subcutaneous: HFD 2.836 g ± 0.636 g vs. CD 0.704 g ± 0.255 g; epididymal: HFD 1.714 g ± 0.441 g vs. CD 0.710 g ± 0.311 g, both n = 38–41, p < 0.001). Diet-induced obesity was accompanied by hyperinsulinemia and impaired oral glucose tolerance, reflected by lower glucose clearance and higher area under the curve (AUC, Table 1, Figure 1D,E).

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