Variations in body weight, food intake and body composition after long-term high-fat diet feeding in C57BL/6J mice

Yang, Yuesuo; Smith, Daniel L.; Keating, Karen D.; Allison, David B.; Nagy, Tim R.

doi:10.1002/oby.20811

Cited by 246 publications

(233 citation statements)

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“…Mice fed the HF diet showed a significant increase in body weight; body fat composition; serum levels of triglycerides, nonesterified fatty acids, total and LDL cholesterol; and increased hepatic steatosis (Figure S1, Table S4). These results are in agreement with previous animal studies showing similar metabolic effects of HF diets [20, 22], which validates our dietary model.…”

Section: Resultssupporting

confidence: 93%

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Human germline hedgehog pathway mutations predispose to fatty liver

Guillen-Sacoto

Martinez

Abe

et al. 2017

Journal of Hepatology

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Background & Aims Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations affecting this pathway. Methods Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2+/−) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. Results Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2+/− mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2+/− mice exposed to high-fat diet. Conclusions Our results indicate that germline mutations disrupting Hh signaling promote liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway.

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Section: Resultssupporting

confidence: 93%

“…A subset of livers was selected for RNA expression profiling, and a subset of pituitary glands was sent for histological evaluation. Because sex differences exist in the response of C57BL/6J mice to dietary models [20], we compared same-sex animals in experimental groups.…”

Section: Methodsmentioning

confidence: 99%

Human germline hedgehog pathway mutations predispose to fatty liver

Guillen-Sacoto

Martinez

Abe

et al. 2017

Journal of Hepatology

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“…Further technological advancements will be needed to study live adult MCs post-sorting in these jet-in-air systems since we observed cell breakage that reduces viability. Furthermore, only male mice were sampled in this study due to the known substantial differences between males and females in growth curves post-weaning 48,49 . Future studies will need to explore if sex variants exist between MC growth and protein content.…”

Section: Discussionmentioning

confidence: 99%

Novel large-particle FACS purification of adult ventricular myocytes reveals accumulation of myosin and actin disproportionate to cell size and proteome in normal post-weaning development

López

Sharma

Ávila

et al. 2017

Journal of Molecular and Cellular Cardiology

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Rationale Quantifying cellular proteins in ventricular myocytes (MCs) is challenging due to tissue heterogeneity and the variety of cell sizes in the heart. In post-weaning cardiac ontogeny, rod-shaped MCs make up the majority of the cardiac mass while remaining a minority of cardiac cells in number. Current biochemical analyses of cardiac proteins do not correlate well the content of MC-specific proteins to cell type or size in normally developing tissue. Objective To develop a new MC-specific large-particle fluorescent-activated cell sorting (LP-FACS) strategy for the purification of adult rod-shaped MCs. This approach is developed to enable growth-scaled measurements per-cell of the MC proteome and sarcomeric protein (i.e. myosin heavy chain (MyHC) and alpha-actin (α-actin)) content. Methods and Results Individual cardiac cells were isolated from 21-94 days old mice. An LP-FACS jet-in-air system with a 200-μm nozzle was defined by the first time to purify adult MCs. Cell-type specific immunophenotyping and sorting yielded ≥95% purity of adult MCs independently of cell morphology and size. This approach excluded other cell types and tissue contaminants from further analysis. MC proteome, MyHC and α-actin proteins were measured in linear biochemical assays normalized to cell numbers. Using the allometric coefficient α, we scaled the MC-specific rate of protein accumulation to growth post-weaning. MC-specific volumes (α=1.02) and global protein accumulation (α=0.94) were proportional (i.e. isometric) to body mass. In contrast, MyHC and α-actin accumulated at a much greater rate (i.e. hyperallometric) than body mass (α= 1.79 and 2.19 respectively) and MC volumes (α= 1.76 and 1.45 respectively). Conclusion Changes in MC proteome and cell volumes measured in LP-FACS purified MCs are proportional to body mass post-weaning. Oppositely, MyHC and α-actin are concentrated more rapidly than what would be expected from MC proteome accumulation, cell enlargement, or animal growth alone. LP-FACS provides a new standard for adult MC purification and an approach to scale the biochemical content of specific proteins or group of proteins per cell in enlarging MCs.

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“…Suman et al observed increased obesity-related factors 12 months after 56-Fe radiation exposure in female C57BL/6J mice (Suman et al 2016). Studies have shown genetic-related (Carter et al 1997;Fearnside et al 2008) and sex-related (Hwang et al 2010;Yang et al 2014) differences in dietinduced body weight increases in various mouse strains. For example, male C57BL/6J mice are more susceptible to dietinduced overweight than females; it also progresses more slowly in females (Yang et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown genetic-related (Carter et al 1997;Fearnside et al 2008) and sex-related (Hwang et al 2010;Yang et al 2014) differences in dietinduced body weight increases in various mouse strains. For example, male C57BL/6J mice are more susceptible to dietinduced overweight than females; it also progresses more slowly in females (Yang et al 2014). However, studies have shown that more women are obese than men (Kanter and Caballero 2012).…”

Section: Introductionmentioning

confidence: 99%

Thoracic gamma irradiation-induced obesity in C57BL/6 female mice

Zhang

Yang

Zhang

et al. 2017

International Journal of Radiation Biology

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Purpose: To investigate the late effects of thoracic region irradiation (TRI) on mouse body weight. Materials and methods: Female C57BL/6 mice were divided into nonirradiated, 5 Gy total body irradiation, 9 Gy sub-total body irradiation, and 12.5 Gy thoracic region irradiation (TRI) groups. Changes in mouse weight were monitored every other week at similar time points for 12 months. The anatomical characteristics of abdominal visceral fat distribution were recorded, and mitochondrial DNA copy number in the hearts and livers and lipid metabolic signaling in the liver were analyzed. Data were analyzed by one-way analysis of variance and a student's t-test. Results: TRI led to a significant increase (p < .001) in body weight that was dependent on time and individuals [42.1% of mice were overweight (50% increase in body weight) 4 months post-TRI and 100% of mice were overweight at 10 months post-TRI]. Gross anatomical features of abdominal visceral fat distribution and storage in radiation-induced overweight/severely overweight mice were similar to those of high fat diet-induced overweight/severely overweight mice. The mitochondrial genome of heart and liver tissues from overweight/severely overweight mice had significantly (p < .05) decreased functional mitochondrial DNA copy number (ratios decreased from 1 to 0.71 or 0.49, respectively) and significantly (p < .05) increased mitochondrial DNA mutations (ratios increased from 1 to 3.21 or 1.83, respectively). CPT1 and IRS2 lipid metabolic signaling was significantly (p < .05-.01) decreased for both mRNA (fold decrease from 1 to 0.60 or 0.55, respectively) and protein (fold decrease from 1 to 0.62 or 0.19, respectively). Conclusions: TRI can cause mice to gain weight. These findings indicate that TRI can result in lipid metabolic abnormalities and provide a model to study the factors that result in these abnormalities. ARTICLE HISTORY

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Variations in body weight, food intake and body composition after long-term high-fat diet feeding in C57BL/6J mice

Cited by 246 publications

References 19 publications

Human germline hedgehog pathway mutations predispose to fatty liver

Human germline hedgehog pathway mutations predispose to fatty liver

Novel large-particle FACS purification of adult ventricular myocytes reveals accumulation of myosin and actin disproportionate to cell size and proteome in normal post-weaning development

Thoracic gamma irradiation-induced obesity in C57BL/6 female mice

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