A high-fat and high-cholesterol diet suppressed white adipose thermogenesis regardless of genotype, while the absence of low-density lipoprotein receptors alleviated diet-induced body fat accumulation.
Does a high-fat and high-cholesterol diet alter thermogenesis and cellular senescence in adipocytes of Ldlr-/- mice?
In a mouse model, a high-fat/high-cholesterol diet suppressed white adipose thermogenesis, and the combination of obesity and atherosclerosis promoted cellular senescence marker expression in brown adipose tissue.
Purpose: Adipose thermogenesis improves metabolic fitness, and cellular senescence is involved in the development of atherosclerosis.This study aimed to demonstrate the effects of obesity and atherosclerosis on thermogenesis and cellular senescence in adipocytes.Methods: C57BL/6J (B6) mice were fed a 10% kcal fat diet (control, CON group) or a 41% kcal fat and 0.21% cholesterol diet (high-fat and high-cholesterol, HFC diet; OB group), and B6.129S7-Ldlr tm1Her /J mice were fed HFC diet (OBA group).Stromal vascular cells were isolated from the white and brown adipose tissue (WAT and BAT) of all the groups and cultured.White and brown primary adipocytes were treated with -adrenergic agonists, including norepinephrine and CL316,243, and thermogenic and cellular senescence gene expressions were measured.Results: Compared to the mice in the CON group, the mice in the OB and OBA groups gained more weight, had more amount of WAT, and lower expression of uncoupling protein 1 (Ucp1) and PRD1-BF1-RIZ1 homologous (PR) domain-containing 16 (Prdm16) in WAT.There was no statistical difference between the CON and OBA groups with respect to the final body weight.-adrenergic agonists upregulated Ucp1 and Pgc1a in white mature adipocytes derived from mice in the CON and OBA groups.Although -adrenergic agonists enhanced Pgc1a expression in brown mature adipocytes from all groups, the upregulation was less pronounced in the cells derived from mice in the OB or OBA group.The mice in the OBA group had higher cyclin-dependent kinase inhibitor 1A (Cdkn1a) and Cdkn2a expression in the BAT, but the gene expression was lower in brown preadipocytes.Conclusion: These data suggest that HFC diet suppressed white adipose thermogenesis regardless of genotype.The absence of low-density lipoprotein receptors alleviated HFC-induced body fat accumulation and maintained the thermogenic response of white adipocytes under stimulation.Although this is speculative, obesity with atherosclerosis may promote the accumulation of senescent immune cells in BAT.
Ock et al. (Wed,) conducted a other in Obesity and atherosclerosis (n=18). High-fat and high-cholesterol (HFC) diet vs. 10% kcal fat diet was evaluated on Thermogenic and cellular senescence gene expressions. A high-fat and high-cholesterol diet suppressed white adipose thermogenesis regardless of genotype, while the absence of low-density lipoprotein receptors alleviated diet-induced body fat accumulation.
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