CREG1 improves diet‐induced obesity via uncoupling protein 1‐dependent manner in mice

2022 ◽  
Author(s):  
Yuki Endo ◽  
Michihiro Hashimoto ◽  
Tatsuya Kusudo ◽  
Tadashi Okada ◽  
Tamaki Takeuchi ◽  
...  
2000 ◽  
Vol 279 (2) ◽  
pp. E356-E365 ◽  
Author(s):  
Patricia M. Watson ◽  
Scott P. Commins ◽  
Rudolph J. Beiler ◽  
Heather C. Hatcher ◽  
Thomas W. Gettys

Obesity-resistant (A/J) and obesity-prone (C57BL/6J) mice were weaned onto low-fat (LF) or high-fat (HF) diets and studied after 2, 10, and 16 wk. Despite consuming the same amount of food, A/J mice on the HF diet deposited less carcass lipid and gained less weight than C57BL/6J mice over the course of the study. Leptin mRNA was increased in white adipose tissue (WAT) in both strains on the HF diet but to significantly higher levels in A/J compared with C57BL/6J mice. Uncoupling protein 1 (UCP1) and UCP2 mRNA were induced by the HF diet in brown adipose tissue (BAT) and WAT of A/J mice, respectively, but not in C57BL/6J mice. UCP1 mRNA was also significantly higher in retroperitoneal WAT of A/J compared with C57BL/6J mice. The ability of A/J mice to resist diet-induced obesity is associated with a strain-specific increase in leptin, UCP1, and UCP2 expression in adipose tissue. The findings indicate that the HF diet does not compromise leptin-dependent regulation of adipocyte gene expression in A/J mice and suggest that maintenance of leptin responsiveness confers resistance to diet-induced obesity.


2020 ◽  
Vol 12 (558) ◽  
pp. eaaz8664 ◽  
Author(s):  
Chih-Hao Wang ◽  
Morten Lundh ◽  
Accalia Fu ◽  
Rókus Kriszt ◽  
Tian Lian Huang ◽  
...  

Brown and brown-like beige/brite adipocytes dissipate energy and have been proposed as therapeutic targets to combat metabolic disorders. However, the therapeutic effects of cell-based therapy in humans remain unclear. Here, we created human brown-like (HUMBLE) cells by engineering human white preadipocytes using CRISPR-Cas9–SAM–gRNA to activate endogenous uncoupling protein 1 expression. Obese mice that received HUMBLE cell transplants showed a sustained improvement in glucose tolerance and insulin sensitivity, as well as increased energy expenditure. Mechanistically, increased arginine/nitric oxide (NO) metabolism in HUMBLE adipocytes promoted the production of NO that was carried by S-nitrosothiols and nitrite in red blood cells to activate endogenous brown fat and improved glucose homeostasis in recipient animals. Together, these data demonstrate the utility of using CRISPR-Cas9 technology to engineer human white adipocytes to display brown fat-like phenotypes and may open up cell-based therapeutic opportunities to combat obesity and diabetes.


2011 ◽  
Vol 300 (6) ◽  
pp. E1146-E1157 ◽  
Author(s):  
Christelle Veyrat-Durebex ◽  
Anne-Laure Poher ◽  
Aurélie Caillon ◽  
Xavier Montet ◽  
Françoise Rohner-Jeanrenaud

Recent studies describe the Lou/C rat as a model of resistance to age- and diet-induced obesity and suggest a preferential channeling of nutrients toward utilization rather than storage under standard feeding conditions. The purpose of the present study was to evaluate lipid metabolism of Lou/C and Wistar rats under a high-fat (HF) diet. Four-month-old male Lou/C and Wistar animals were submitted to a 40% HF diet for 5–9 wk. Evolution of food intake, body weight, and body composition, hormonal parameters, and expression of key transcription factors and enzymes involved in lipid metabolism were determined. Wistar rats developed obesity after 5 wk of HF diet, as previously described. Among the various parameters measured, accumulation of intraperitoneal fat was particularly evident in HF-fed Wistar rats. In these animals, thermogenesis was, however, stimulated as a likely compensatory mechanism against the development of obesity. On the contrary, Lou/C animals failed to develop obesity under such a diet, and intraperitoneal fat, not including epididymal and retroperitoneal fat depots, was virtually absent. Enzyme measurements confirmed lipid utilization rather than storage, which was accompanied by the striking emergence of uncoupling protein-1, characteristic of brown adipocytes, in white adipose tissue, particularly in the subcutaneous depot.


2015 ◽  
Vol 19 ◽  
pp. 1-9 ◽  
Author(s):  
Yuko Okamatsu-Ogura ◽  
Ayumi Tsubota ◽  
Kana Ohyama ◽  
Yoshihito Nogusa ◽  
Masayuki Saito ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Susanne Keipert ◽  
Dominik Lutter ◽  
Bjoern O. Schroeder ◽  
Daniel Brandt ◽  
Marcus Ståhlman ◽  
...  

AbstractUncoupling protein 1 (UCP1) executes thermogenesis in brown adipose tissue, which is a major focus of human obesity research. Although the UCP1-knockout (UCP1 KO) mouse represents the most frequently applied animal model to judge the anti-obesity effects of UCP1, the assessment is confounded by unknown anti-obesity factors causing paradoxical obesity resistance below thermoneutral temperatures. Here we identify the enigmatic factor as endogenous FGF21, which is primarily mediating obesity resistance. The generation of UCP1/FGF21 double-knockout mice (dKO) fully reverses obesity resistance. Within mild differences in energy metabolism, urine metabolomics uncover increased secretion of acyl-carnitines in UCP1 KOs, suggesting metabolic reprogramming. Strikingly, transcriptomics of metabolically important organs reveal enhanced lipid and oxidative metabolism in specifically white adipose tissue that is fully reversed in dKO mice. Collectively, this study characterizes the effects of endogenous FGF21 that acts as master regulator to protect from diet-induced obesity in the absence of UCP1.


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