Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity

1994 ◽  
Vol 266 (5) ◽  
pp. R1423-R1428 ◽  
Author(s):  
G. P. Eberhart ◽  
D. B. West ◽  
C. N. Boozer ◽  
R. L. Atkinson
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Transport ◽  
High Fat Diet ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
High Fat ◽  
Adipose Depot ◽  
Adipocyte Cell ◽  
Dietary Obesity ◽  
Lipid Stores

We evaluated insulin sensitivity in epididymal adipocytes from two mouse strains shown to be either sensitive (AKR/J, n = 14) or resistant (SWR/J, n = 12) to the development of obesity when fed a high-fat diet. Half of each strain was fed a chow (CH) diet (12% fat), and half received a sweetened condensed milk (CM) diet (33% fat). After 1 wk, epididymal adipose depots were removed and digested with collagenase, and glucose transport was measured with labeled 2-deoxyglucose. Plasma glucose and insulin were slightly higher in AKR/J than SWR/J mice (glucose: 139.7 vs. 118.8 mg/dl, P < 0.06; insulin: 3.45 vs. 2.99 ng/ml, P < 0.04). One week of high-fat feeding increased adipose depot mass and carcass lipid in both strains to approximately the same extent. Adipocytes from AKR/J mice had greater insulin-stimulated glucose transport compared with SWR/J mice at both submaximal and maximal insulin levels (P < 0.0001). Short-term feeding of the high-fat diet increased AKR/J adipocyte insulin sensitivity but decreased the sensitivity of SWR/J adipocytes to insulin. The differences in adipocyte insulin sensitivity between strains were not explained by differences in adipocyte cell size. Access to the high-fat CM diet for 12 wk increased total dissected adipose depot size by 209% in the AKR/J mice and 82% in the SWR/J mice. These data clearly demonstrate that the two strains differ in adipocyte insulin sensitivity as well as sensitivity to dietary obesity. Increased adipocyte insulin sensitivity could contribute to a predisposition to increase adipose tissue lipid stores with diets high in fat content.

scholarly journals ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 386 ◽  
Author(s):  
Ayca Dogan ◽  
Peter Lasch ◽  
Christina Neuschl ◽  
Marion K Millrose ◽  
Rudi Alberts ◽  
...  
Keyword(s):  
Ftir Spectroscopy ◽  
Recombinant Inbred ◽  
High Fat Diet ◽  
Inbred Mouse ◽  
Tissue Response ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
High Fat ◽  
Recombinant Inbred Mouse

scholarly journals Multiple trait measurements in 43 inbred mouse strains capture the phenotypic diversity characteristic of human populations

2007 ◽  
Vol 102 (6) ◽  
pp. 2369-2378 ◽  
Author(s):  
Karen L. Svenson ◽  
Randy Von Smith ◽  
Phyllis A. Magnani ◽  
Heather R. Suetin ◽  
Beverly Paigen ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Phenotypic Diversity ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Human Populations ◽  
Large Set ◽  
Inbred Mouse Strains ◽  
High Fat ◽  
Mineral Density

The breadth of genetic and phenotypic variation among inbred strains is often underappreciated because assessments include only a limited number of strains. Evaluation of a larger collection of inbred strains provides not only a greater understanding of this variation but collectively mimics much of the variation observed in human populations. We used a high-throughput phenotyping protocol to measure females and males of 43 inbred strains for body composition (weight, fat, lean tissue mass, and bone mineral density), plasma triglycerides, high-density lipoprotein and total cholesterol, glucose, insulin, and leptin levels while mice consumed a high-fat, high-cholesterol diet. Mice were fed a chow diet until they were 6–8 wk old and then fed the high-fat diet for an additional 18 wk. As expected, broad phenotypic diversity was observed among these strains. Significant variation between the sexes was also observed for most traits measured. Additionally, the response to the high-fat diet differed considerably among many strains. By the testing of such a large set of inbred strains for many traits, multiple phenotypes can be considered simultaneously and thereby aid in the selection of certain inbred strains as models for complex human diseases. These data are publicly available in the web-accessible Mouse Phenome Database ( http://www.jax.org/phenome ), an effort established to promote systematic characterization of biochemical and behavioral phenotypes of commonly used and genetically diverse inbred mouse strains. Data generated by this effort builds on the value of inbred mouse strains as a powerful tool for biomedical research.

scholarly journals Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice

2010 ◽  
Vol 42A (4) ◽  
pp. 228-234 ◽  
Author(s):  
Renhua H. Li ◽  
Gary A. Churchill
Keyword(s):  
High Fat Diet ◽  
Genetic Factors ◽  
Inbred Mouse ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Mouse Strains ◽  
High Fat ◽  
Expression Of Genes ◽  
Genetic Buffering

Stressful environmental factors, such as a high-fat diet, can induce responses in the expression of genes that act to maintain physiological homeostasis. We observed variation in plasma concentrations of high-density lipoprotein (HDL) cholesterol across inbred mouse strains in response to high dietary fat intake. Several strains, including C57BL/6J, have stable levels of plasma HDL independent of diet, whereas other strains, including DBA2/J, show marked changes in plasma HDL. To explore this phenomenon further, we used publicly available data from a C57BL/6J × DBA/2J intercross to identify genetic factors that associate with HDL under high-fat diet conditions. Our analysis identified an epistatic interaction that plays a role in the buffering of HDL levels in C57BL/6J mice, and we have identified Arl4d as a candidate gene that mediates this effect. Structural modeling further elucidates the interaction of genetic factors that contribute to the robustness of HDL in response to high-fat diet in the C57BL/6J strain.

scholarly journals Divergent compensatory responses to high-fat diet between C57BL6/J and C57BLKS/J inbred mouse strains

2013 ◽  
Vol 305 (12) ◽  
pp. E1495-E1511 ◽  
Author(s):  
Emily K. Sims ◽  
Masayuki Hatanaka ◽  
David L. Morris ◽  
Sarah A. Tersey ◽  
Tatsuyoshi Kono ◽  
...  
Keyword(s):  
Weight Gain ◽  
Mouse Models ◽  
Fat Mass ◽  
High Fat Diet ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Insulin Production ◽  
High Fat ◽  
Β Cell

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 diet- and 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 PPARγ 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.

scholarly journals High-fat diet impairs the effects of a single bout of endurance exercise on glucose transport and insulin sensitivity in rat skeletal muscle

Metabolism ◽  
2007 ◽  
Vol 56 (12) ◽  
pp. 1719-1728 ◽  
Author(s):  
Satsuki Tanaka ◽  
Tatsuya Hayashi ◽  
Taro Toyoda ◽  
Taku Hamada ◽  
Yohei Shimizu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Endurance Exercise ◽  
High Fat Diet ◽  
High Fat ◽  
Rat Skeletal Muscle ◽  
Single Bout

Metabolic differences between obesity-prone and obesity-resistant rats

1990 ◽  
Vol 259 (6) ◽  
pp. R1103-R1110 ◽  
Author(s):  
S. Chang ◽  
B. Graham ◽  
F. Yakubu ◽  
D. Lin ◽  
J. C. Peters ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Relative Proportion ◽  
Fat Oxidation ◽  
Fat Intake ◽  
High Fat ◽  
Lower Plasma ◽  
Physiological Variables ◽  
Dietary Obesity

We compared, across several physiological variables, rats most and least susceptible to develop obesity when given a high-fat diet. After 4 wk of eating a high-fat diet (60% of calories from fat), rats in the upper (obesity prone, OP) and lower (obesity resistant, OR) quartiles for weight gain were further studied. OP rats ate significantly more than OR rats, but this did not completely explain differences in their susceptibility to dietary obesity. No differences in 24-h energy expenditure were found between groups. OR rats had a significantly lower 24-h respiratory quotient, indicative of a greater relative proportion of fat oxidation and lower plasma levels of free fatty acids (FFA) than OP rats. Thus the ability to avoid dietary obesity produced by a high-fat diet may depend on an ability to increase fat oxidation in response to increased fat intake. Insulin sensitivity, measured by a euglycemic insulin clamp, was significantly higher in OR than OP rats. We cannot determine from these data whether insulin resistance developed as a consequence of elevated FFA levels or whether the ability to oxidize FFA declined as a result of development of insulin resistance. In summary, we propose that rats able to resist becoming obese on a high-fat diet have the ability to adjust the composition of fuel oxidized to the fuel composition of the diet with a minimum increase in body fat. The specific mechanisms by which this occurs are unknown but may be related to effects of diet on insulin sensitivity.

scholarly journals Differential effect of inbred mouse strain (C57BL/6, DBA/2, 129T2) on insulin secretory function in response to a high fat diet

2005 ◽  
Vol 187 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Sofianos Andrikopoulos ◽  
Christine M Massa ◽  
Kathryn Aston-Mourney ◽  
Alexandra Funkat ◽  
Barbara C Fam ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
The Other ◽  
Mouse Strains ◽  
Secretory Function ◽  
High Fat ◽  
Glucose Levels ◽  
Fasting Plasma ◽  
First Phase Insulin Secretion

The increasing production of genetically-modified mouse models has necessitated studies to determine the inherent physiological characteristics of commonly used mouse strains. In this study we examined insulin secretory function in response to an intravenous bolus of glucose or glucose plus arginine in anesthetized C57BL/6, DBA/2 and 129T2 mice fed either a control or high fat diet for 6 weeks. The results show that 129T2 mice had higher fasting plasma glucose levels and lower fasting plasma insulin levels compared with C57BL/6 and DBA/2 mice regardless of diet. Furthermore, 129T2 mice were glucose intolerant and secreted significantly less insulin in response to glucose and glucose plus arginine irrespective of diet compared with the other two strains of mice. DBA/2 mice hypersecreted insulin in response to glucose and glucose plus arginine compared with C57BL/6 and 129T2 mice. Moreover while first phase insulin secretion was appropriately increased in response to the high fat diet in C57BL/6 and 129T2 mice, this was not the case for DBA/2 mice. Mean islet area was decreased in response to a high fat diet in DBA/2 mice, while there was no dietary effect on the other two strains. This study highlights the inherent genetic differences that exist among seemingly normal strains of mice that are commonly used to make transgenic and knockout mice. Understanding these differences will provide researchers with the information to choose the appropriate genetic background on which to express their particular genetic alteration.

High-fat feeding disrupts daily eating behavior rhythms in obesity-prone but not in obesity-resistant male inbred mouse strains

2021 ◽  
Author(s):  
Tiffany N Buckley ◽  
Oluwabukola Omotola ◽  
Luke A Archer ◽  
Cameron R Rostron ◽  
Ellora P Kamineni ◽  
...  
Keyword(s):  
Eating Behavior ◽  
High Fat Diet ◽  
Inbred Mouse ◽  
Daily Rhythm ◽  
Mouse Strains ◽  
Male Mice ◽  
High Fat ◽  
Late Night ◽  
Diet Induced Obesity ◽  
Fat Feeding

Abnormal meal timing, like skipping breakfast and late-night snacking, is associated with obesity in humans. Disruption of daily eating rhythms also contributes to obesity in mice. When fed high-fat diet, male C57BL/6J mice have disrupted eating behavior rhythms and they become obese. In contrast to obesity-prone C57BL/6J mice, some inbred strains of mice are resistant to high-fat diet-induced obesity. In this study, we sought to determine whether there are distinct effects of high-fat feeding on daily eating behavior rhythms in obesity-prone and obesity-resistant male mice. Male obesity-prone (C57BL/6J and 129X1/SvJ) and obesity-resistant (SWR/J and BALB/cJ) mice were fed low-fat diet or high-fat diet for 6 weeks. Consistent with previous studies, obesity-prone male mice gained more weight and adiposity during high-fat diet feeding than obesity-resistant male mice. The amplitude of the daily rhythm of eating behavior was markedly attenuated in male obesity-prone mice fed high-fat diet, but not in obesity-resistant males. In contrast, high-fat feeding did not differentially affect locomotor activity rhythms in obesity-prone and obesity-resistant male mice. Together, these data suggest that regulation of the daily rhythm of eating may underlie propensity to develop diet-induced obesity in male mice.

scholarly journals Effects of atherogenic diet on hepatic gene expression across mouse strains

2009 ◽  
Vol 39 (3) ◽  
pp. 172-182 ◽  
Author(s):  
Keith R. Shockley ◽  
David Witmer ◽  
Sarah L. Burgess-Herbert ◽  
Beverly Paigen ◽  
Gary A. Churchill
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Metabolic Response ◽  
Cholesterol Biosynthesis ◽  
Inbred Mouse ◽  
Atherogenic Diet ◽  
Chromosome 17 ◽  
Mouse Strains ◽  
High Fat ◽  
Low Fat

Diets high in fat and cholesterol are associated with increased obesity and metabolic disease in mice and humans. To study the molecular basis of the metabolic response to dietary fat, 10 inbred strains of mice were fed atherogenic high-fat and control low-fat diets. Liver gene expression and whole animal phenotypes were measured and analyzed in both sexes. The effects of diet, strain, and sex on gene expression were determined irrespective of complex processes, such as feedback mechanisms, that could have mediated the genomic responses. Global gene expression analyses demonstrated that animals of the same strain and sex have similar transcriptional profiles on a low-fat diet, but strains may show considerable variability in response to high-fat diet. Functional profiling indicated that high-fat feeding induced genes in the immune response, indicating liver damage, and repressed cholesterol biosynthesis. The physiological significance of the transcriptional changes was confirmed by a correlation analysis of transcript levels with whole animal phenotypes. The results found here were used to confirm a previously identified quantitative trait locus on chromosome 17 identified in males fed a high-fat diet in two crosses, PERA × DBA/2 and PERA × I/Ln. The gene expression data and phenotype data have been made publicly available as an online tool for exploring the effects of atherogenic diet in inbred mouse strains ( http://cgd-array.jax.org/DietStrainSurvey ).

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