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White adipose tissue (WAT) is a complex organ that plays a central role in systemic energy balance through its interrelated metabolic, endocrine, and immune functions. Adipocytes, the parenchymal cells of adipose tissue, have diverse functions that include storage and mobilization of lipids. They also release endocrine signals that report energy status to the brain, regulating metabolic functions in peripheral organs. Importantly, the metabolic character of white adipocytes is flexible, with cells capable of assuming distinct anabolic and catabolic/thermogenic phenotypes, often within the same adipose tissue depot

Elizabeth A. Rondini, Vanesa D. Ramseyer, Rayanne B. Burl, Roger Pique-Regi, James G. Granneman

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Cyp2c-deficiency depletes muricholic acids and protects against high-fat diet-induced obesity in male mice but promotes liver damage

Antwi-Boasiako Oteng, Sei Higuchi, Alexander S. Banks, Rebecca A. Haeusler

Objective

Murine-specific muricholic acids (MCAs) are reported to protect against obesity and associated metabolic disorders. However, the response of mice with genetic depletion of MCA to an obesogenic diet has not been evaluated. We used Cyp2c-deficient (Cyp2c−/−) mice, which lack MCAs and thus have a human-like bile acid(BA) profile, to directly investigate the potential role of MCAs in diet-induced obesity.

Methods

Male and female Cyp2c−/− mice and wild-type (WT) littermate controls were fed a standard chow diet or a high-fat diet (HFD) for 18 weeks. We measured BA composition from a pool of liver, gallbladder, and intestine, as well as weekly body weight, food intake, lean and fat mass, systemic glucose homeostasis, energy expenditure, intestinal lipid absorptionfecal lipid, and energy content.

Results

Cyp2c-deficiency depleted MCAs and caused other changes in BA composition, namely a decrease in the ratio of 12α-hydroxylated (12α-OH) BAs to non-12α-OH BAs, without altering the total BA levels. While WT male mice became obese after HFD feeding, Cyp2c−/− male mice were protected from obesity and associated metabolic dysfunctions. Cyp2c−/− male mice also showed reduced intestinal lipid absorption and increased lipid excretion, which was reversed by oral gavage with the 12α-OH BA and taurocholic acid (TCA). Cyp2c−/− mice also showed increased liver damage, which appeared stronger in females.

Conclusions

MCA does not protect against diet-induced obesity but may protect against liver injury. Reduced lipid absorption in Cyp2c-deficient male mice is potentially due to a reduced ratio of 12α-OH/non-12α-OH BAs.

Cyp2c-deficiency depletes muricholic acids and protects against high-fat diet-induced obesity in male mice but promotes liver damage

Antwi-Boasiako Oteng, Sei Higuchi, Alexander S. Banks, Rebecca A. Haeusler

Objective

Murine-specific muricholic acids (MCAs) are reported to protect against obesity and associated metabolic disorders. However, the response of mice with genetic depletion of MCA to an obesogenic diet has not been evaluated. We used Cyp2c-deficient (Cyp2c−/−) mice, which lack MCAs and thus have a human-like bile acid(BA) profile, to directly investigate the potential role of MCAs in diet-induced obesity.

Methods

Male and female Cyp2c−/− mice and wild-type (WT) littermate controls were fed a standard chow diet or a high-fat diet (HFD) for 18 weeks. We measured BA composition from a pool of liver, gallbladder, and intestine, as well as weekly body weight, food intake, lean and fat mass, systemic glucose homeostasis, energy expenditure, intestinal lipid absorptionfecal lipid, and energy content.

Results

Cyp2c-deficiency depleted MCAs and caused other changes in BA composition, namely a decrease in the ratio of 12α-hydroxylated (12α-OH) BAs to non-12α-OH BAs, without altering the total BA levels. While WT male mice became obese after HFD feeding, Cyp2c−/− male mice were protected from obesity and associated metabolic dysfunctions. Cyp2c−/− male mice also showed reduced intestinal lipid absorption and increased lipid excretion, which was reversed by oral gavage with the 12α-OH BA and taurocholic acid (TCA). Cyp2c−/− mice also showed increased liver damage, which appeared stronger in females.

Conclusions

MCA does not protect against diet-induced obesity but may protect against liver injury. Reduced lipid absorption in Cyp2c-deficient male mice is potentially due to a reduced ratio of 12α-OH/non-12α-OH BAs.

2020 impact factor: 7.4

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