Abstract
We previously found that senescence of cluster of differentiation 4 (CD4) T cells is accelerated in the visceral adipose tissue (VAT) of mice with diet-induced obesity (DIO) due to a high-fat diet (HFD), and that these senescent-associated T cells cause chronic inflammation of visceral adipose tissue through secretion of osteopontin, provoking systemic insulin resistance. In this study, we examined whether the development of chronic inflammation and senescence-associated T cells in VAT of DIO mice was improved by long-term weight loss after switching to normal chow (NC) or by administration of a sodium glucose cotransporter 2 inhibitor (tofogliflozin). Wild-type mice were fed an HFD for 26 weeks from 4 weeks old. At 30 weeks of age, half of these DIO mice were switched to NC with or without 0.005% tofogliflozin for 38 weeks. The other mice remained on the HFD with or without 0.005% tofogliflozin for 38 weeks. When DIO mice were switched to NC, their weight decreased to that of mice kept on NC since weaning. After 38 weeks (68 weeks of age), chronic inflammation of the VAT subsided with disappearance of senescence-associated T cells. In the HFD groups, the carbohydrate intake per mouse was half or less of that in the NC group, and urinary glucose excretion by the effect of tofogliflozin was lower in the HFD mice than in the NC mice. Mice that remained on the HFD showed no improvement in chronic inflammation in VAT, possibly because urinary glucose excretion was not sufficiently promoted by tofogliflozin due to the low carbohydrate intake. Thus, no improvement in glucose metabolism or weight loss was observed in these mice.
Highlights
Accumulation of visceral fat causes hypertension, diabetes mellitus, and dyslipidemia, leading to the development of cardiovascular disease, chronic kidney disease, or cancer over time [1,2,3,4,5,6]
When diet-induced obesity (DIO) mice fed an high-fat diet (HFD) until 30 weeks of age were switched to normal chow (NC), their food intake calculated from two cages per group tended to decrease transiently and their weight declined (Fig 1A and 1B)
Hemoglobin A1c (HbA1c), fasting blood glucose, insulin levels and total cholesterol (TC) were significantly improved compared to the HFD (Fig 2D–2F), there were no significant difference in non-fasting glucose and insulin level (Fig 2G)
Summary
Accumulation of visceral fat causes hypertension, diabetes mellitus, and dyslipidemia, leading to the development of cardiovascular disease, chronic kidney disease, or cancer over time [1,2,3,4,5,6]. These processes associated with the metabolic syndrome are called the metabolic. This funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.