High fat feeding unmasks variable insulin responses in male C57BL/6 mouse substrains

Hull, Rebecca L.; Willard, Joshua R.; Struck, Matthias D; Barrow, Breanne M.; Brar, Gurkirat S; Andrikopoulos, Sofianos; Zraika, Sakeneh

doi:10.1530/joe-16-0377

Cited by 40 publications

(50 citation statements)

References 31 publications

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“…Furthermore, mice were housed at different institutes. This supports recent reports highlighting that metabolic differences can exist between substrains of C57Bl/6J mice (Hull et al 2017).…”

Section: :3supporting

confidence: 92%

Resolution of glucose intolerance in long-term high-fat, high-sucrose-fed mice

Kowalski

Kraakman

Mason

et al. 2017

Journal of Endocrinology

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The high-fat, high-sucrose diet (HFSD)-fed C57Bl/6 mouse is a widely used model of prediabetes. However, studies typically implement a relatively short dietary intervention lasting between 4 and 16 weeks; as a result, little is known about how a long-term HFSD influences the metabolic profile of these mice. Therefore, the aim of this investigation was to examine the effects of consuming a HFSD for 42 weeks on the development of hyperinsulinaemia and glucose intolerance in male C57Bl/6 mice. Two cohorts of HFSD mice were studied at independent institutes and they underwent an oral glucose tolerance test (OGTT) with measures of plasma insulin and free fatty acids (FFA). Age-matched chow-fed control mice were also studied. The HFSD-fed mice were hyperinsulinaemic and grossly obese, being over 25 g heavier than chow-fed mice, which was due to a marked expansion of subcutaneous adipose tissue. This was associated with a 3-fold increase in liver lipid content. Glucose tolerance, however, was either the same or better than control mice due to the preservation of glucose disposal as revealed by a dynamic stable isotope-labelled OGTT. In addition, plasma FFAs were suppressed to lower levels in HFSD mice during the OGTT. In conclusion, we have made the paradoxical observation that long-term HFSD feeding results in the resolution of glucose intolerance in the C57Bl/6 mouse. Mechanistically, we propose that the gross expansion of subcutaneous adipose tissue increases the glucose disposal capacity of the HFSD-fed mouse, which overcomes the prevailing insulin resistance to improve glucose tolerance.

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Section: :3supporting

confidence: 92%

Resolution of glucose intolerance in long-term high-fat, high-sucrose-fed mice

Kowalski

Kraakman

Mason

et al. 2017

Journal of Endocrinology

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“…On the other hand, according to our results, a recent study described that high-fat diet feeding for 7 months did not alter cardiac function measuring by echocardiography in the same mice strain 16 . An explanation for the differences in cardiac susceptibility to high fat diet between published studies could be due to the use of different substrains of C57BL/6 17 , 18 .…”

Section: Discussionmentioning

confidence: 98%

Circulating miR-19b and miR-181b are potential biomarkers for diabetic cardiomyopathy

Copier

León

Fernández

et al. 2017

Sci Rep

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Diabetic cardiomyopathy is characterized by metabolic changes in the myocardium that promote a slow and silent dysfunction of muscle fibers, leading to myocardium remodelling and heart failure, independently of the presence of coronary artery diseases or hypertension. At present, no imaging methods allow an early diagnosis of this disease. Circulating miRNAs in plasma have been proposed as biomarkers in the prognosis of several cardiac diseases. This study aimed to determine whether circulating miRNAs could be potential biomarkers of diabetic cardiomyopathy. Mice that were fed with a high fat diet for 16 months, showed metabolic syndrome manifestations, cardiac hypertrophy (without hypertension) and a progressive cardiac function decline. At 16 months, when maximal degree of cardiac dysfunction was observed, 15 miRNAs from a miRNA microarray screening in myocardium were selected. Then, selected miRNAs expression in myocardium (at 4 and 16 months) and plasma (at 4, 12 and 16 months) were measured by RT-qPCR. Circulating miR-19b-3p and miR-181b-5p levels were associated with myocardium levels during the development of diabetic cardiomyopathy (in terms of cardiac dysfunction), suggesting that these miRNAs could be suitable biomarkers of this disease in asymptomatic diabetic patients.

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“…Four weeks after vehicle or STZ injections, intraperitoneal insulin tolerance tests (1 IU/kg, ITTs) were performed in conscious mice fasted for 3.5 hours [ 8 ]. Tail vein blood was collected at 0, 15, 30, 45, and 60 minutes post insulin administration for glucose measurement.…”

Section: Methodsmentioning

confidence: 99%

“…Another widely used model is the high fat-fed C57BL/6 mouse, which exhibits numerous aspects of the diabetic phenotype typically seen in obese humans, including insulin resistance and hyperinsulinemia [ 5 , 6 ]. However, diet-induced obese mice often do not demonstrate reduced glucose-mediated insulin secretion [ 7 , 8 ], as is characteristic of human T2D, and, like db/db and ob/ob mice, exhibit expansion of β -cell mass.…”

Section: Introductionmentioning

confidence: 99%

A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes

Parilla

Willard

Barrow

et al. 2018

Journal of Diabetes Research

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Loss of first-phase insulin release is an early pathogenic feature of type 2 diabetes (T2D). Various mouse models exist to study T2D; however, few recapitulate the early β-cell defects seen in humans. We sought to develop a nongenetic mouse model of T2D that exhibits reduced first-phase insulin secretion without a significant deficit in pancreatic insulin content. C57BL/6J mice were fed 10% or 60% fat diet for three weeks, followed by three consecutive, once-daily intraperitoneal injections of the β-cell toxin streptozotocin (STZ; 30, 50, or 75 mg/kg) or vehicle. Four weeks after injections, the first-phase insulin response to glucose was reduced in mice when high-fat diet was combined with 30, 50, or 75 mg/kg STZ. This was accompanied by diminished second-phase insulin release and elevated fed glucose levels. Further, body weight gain, pancreatic insulin content, and β-cell area were decreased in high fat-fed mice treated with 50 and 75 mg/kg STZ, but not 30 mg/kg STZ. Low fat-fed mice were relatively resistant to STZ, with the exception of reduced pancreatic insulin content and β-cell area. Together, these data demonstrate that in high fat-fed mice, three once-daily injections of 30 mg/kg STZ produces a model of β-cell failure without insulin deficiency that may be useful in studies investigating the etiology and progression of human T2D.

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High fat feeding unmasks variable insulin responses in male C57BL/6 mouse substrains

Cited by 40 publications

References 31 publications

Resolution of glucose intolerance in long-term high-fat, high-sucrose-fed mice

Resolution of glucose intolerance in long-term high-fat, high-sucrose-fed mice

Circulating miR-19b and miR-181b are potential biomarkers for diabetic cardiomyopathy

A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes

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