Divergent compensatory responses to high-fat diet between C57Bl6/J and c57BlKS/J inbred mouse strains

Emily K. Sims, Masayuki Hatanaka, David L. Morris, Sarah A. Tersey, Tatsuyoshi Kono, Zunaira Z. Chaudry, Kathleen H. Day, Dan R. Moss, Natalie D. Stull, Raghu Mirmira, Carmella Evans-Molina

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) are polygenic disorders with complex pathophysiologies; recapitulating them with mouse models is challenging. Despite 70% genetic homology, C57BL/6J (BL6) and C57BLKS/J (BLKS) inbred mouse strains differ in response to dietand genetic-induced obesity. We hypothesized these differences would yield insight into IGT and T2DM susceptibility and response to pharmacological therapies. To this end, male 8-wk-old BL6 and BLKS mice were fed normal chow (18% kcal from fat), high-fat diet (HFD; 42% kcal from fat), or HFD supplemented with the PPAR agonist pioglitazone (PIO; 140 mg PIO/kg diet) for 16 wk. Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were undertaken. BL6 mice gained weight and adiposity in response to HFD, leading to peripheral insulin resistance that was met with increased β-cell proliferation and insulin production. By contrast, BLKS mice responded to HFD by restricting food intake and increasing activity. These behavioral responses limited weight gain and protected against HFD-induced glucose intolerance, which in this strain was primarily due to β-cell dysfunction. PIO treatment did not affect HFD-induced weight gain in BL6 mice, and decreased visceral fat mass, whereas in BLKS mice PIO increased total fat mass without improving visceral fat mass. Differences in these responses to HFD and effects of PIO reflect divergent human responses to a Western lifestyle and underscore the careful consideration needed when choosing mouse models of diet-induced obesity and diabetes treatment.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume305
Issue number12
DOIs
StatePublished - Dec 15 2013

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Inbred Strains Mice
High Fat Diet
Glucose Intolerance
Intra-Abdominal Fat
pioglitazone
Fats
Weight Gain
Obesity
Insulin
Diet
Peroxisome Proliferator-Activated Receptors
Adiposity
Body Composition
Vascular Resistance
Type 2 Diabetes Mellitus
Energy Metabolism
Insulin Resistance
Life Style
Pancreas
Homeostasis

Keywords

  • C57BL/6J
  • C57BLKS/J
  • Diet-induced obesity
  • Mouse models of T2DM
  • Pioglitazone

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Divergent compensatory responses to high-fat diet between C57Bl6/J and c57BlKS/J inbred mouse strains. / Sims, Emily K.; Hatanaka, Masayuki; Morris, David L.; Tersey, Sarah A.; Kono, Tatsuyoshi; Chaudry, Zunaira Z.; Day, Kathleen H.; Moss, Dan R.; Stull, Natalie D.; Mirmira, Raghu; Evans-Molina, Carmella.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 305, No. 12, 15.12.2013.

Research output: Contribution to journalArticle

Sims, Emily K. ; Hatanaka, Masayuki ; Morris, David L. ; Tersey, Sarah A. ; Kono, Tatsuyoshi ; Chaudry, Zunaira Z. ; Day, Kathleen H. ; Moss, Dan R. ; Stull, Natalie D. ; Mirmira, Raghu ; Evans-Molina, Carmella. / Divergent compensatory responses to high-fat diet between C57Bl6/J and c57BlKS/J inbred mouse strains. In: American Journal of Physiology - Endocrinology and Metabolism. 2013 ; Vol. 305, No. 12.
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abstract = "Impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) are polygenic disorders with complex pathophysiologies; recapitulating them with mouse models is challenging. Despite 70{\%} genetic homology, C57BL/6J (BL6) and C57BLKS/J (BLKS) inbred mouse strains differ in response to dietand genetic-induced obesity. We hypothesized these differences would yield insight into IGT and T2DM susceptibility and response to pharmacological therapies. To this end, male 8-wk-old BL6 and BLKS mice were fed normal chow (18{\%} kcal from fat), high-fat diet (HFD; 42{\%} kcal from fat), or HFD supplemented with the PPAR agonist pioglitazone (PIO; 140 mg PIO/kg diet) for 16 wk. Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were undertaken. BL6 mice gained weight and adiposity in response to HFD, leading to peripheral insulin resistance that was met with increased β-cell proliferation and insulin production. By contrast, BLKS mice responded to HFD by restricting food intake and increasing activity. These behavioral responses limited weight gain and protected against HFD-induced glucose intolerance, which in this strain was primarily due to β-cell dysfunction. PIO treatment did not affect HFD-induced weight gain in BL6 mice, and decreased visceral fat mass, whereas in BLKS mice PIO increased total fat mass without improving visceral fat mass. Differences in these responses to HFD and effects of PIO reflect divergent human responses to a Western lifestyle and underscore the careful consideration needed when choosing mouse models of diet-induced obesity and diabetes treatment.",
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AU - Kono, Tatsuyoshi

AU - Chaudry, Zunaira Z.

AU - Day, Kathleen H.

AU - Moss, Dan R.

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AU - Mirmira, Raghu

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