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Sodium glucose cotransporter 2 inhibitor dapagliflozin depressed adiposity and ameliorated hepatic steatosis in high-fat diet induced obese mice.

ABSTRACT: With the increasing obesity prevalence, the rates of obesity-related diseases, including type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases, have increased dramatically. Dapagliflozin, one of the sodium glucose cotransporter inhibitors, not only exerts hypoglycaemic effects through increasing urinary glucose excretion but alsoreprograms the metabolic system, leading to benefits in metabolic and cardiovascular diseases. In this study, pre-established obese mice on a high-fat diet were given dapagliflozin by gavage for fourweeks. It showed that dapagliflozin can enhance fat utilization and browning of adipose tissue and improve local oxidative stress, thus inhibiting fat accumulation and hepatic steatosis without disturbance in body weight or plasma glycolipid level. Overall, our study highlights the potential clinical application of SGLT2 inhibition in the prevention of obesity and related metabolic diseases, such as insulin resistance, NAFLD, and diabetes.

SUBMITTER: Han T

PROVIDER: S-EPMC8475578 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Sodium glucose cotransporter 2 inhibitor dapagliflozin depressed adiposity and ameliorated hepatic steatosis in high-fat diet induced obese mice.

Han Tuo T Fan Yajie Y Gao Jie J Fatima Mahreen M Zhang Yali Y Ding Yiming Y Bai Liang L Wang Congxia C

Adipocyte 20211201 1

With the increasing obesity prevalence, the rates of obesity-related diseases, including type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases, have increased dramatically. Dapagliflozin, one of the sodium glucose cotransporter inhibitors, not only exerts hypoglycaemic effects through increasing urinary glucose excretion but alsoreprograms the metabolic system, leading to benefits in metabolic and cardiovascular diseases. In this study, pre-established obese mic ...[more]

PMID: 34550043

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Project description:ObjectiveTofogliflozin, a highly selective inhibitor of sodium/glucose cotransporter 2 (SGLT2), induces urinary glucose excretion (UGE), improves hyperglycemia and reduces body weight in patients with Type 2 diabetes (T2D). The mechanisms of tofogliflozin on body weight reduction were investigated in detail with obese and diabetic animal models.MethodsDiet-induced obese (DIO) rats and KKAy mice (a mouse model of diabetes with obesity) were fed diets containing tofogliflozin. Body weight, body composition, biochemical parameters and metabolic parameters were evaluated.ResultsIn DIO rats tofogliflozin was administered for 9 weeks, UGE was induced and body weight gain was attenuated. Body fat mass decreased without significant change in bone mass or lean body mass. Food consumption (FC) increased without change in energy expenditure, and deduced total calorie balance (deduced total calorie balance=FC-UGE-energy expenditure) decreased. Respiratory quotient (RQ) and plasma triglyceride (TG) level decreased, and plasma total ketone body (TKB) level increased. Moreover, plasma leptin level, adipocyte cell size and proportion of CD68-positive cells in mesenteric adipose tissue decreased. In KKAy mice, tofogliflozin was administered for 3 or 5 weeks, plasma glucose level and body weight gain decreased together with a reduction in liver weight and TG content without a reduction in body water content. Combination therapy with tofogliflozin and pioglitazone suppressed pioglitazone-induced body weight gain and reduced glycated hemoglobin level more effectively than monotherapy with either pioglitazone or tofogliflozin alone.ConclusionBody weight reduction with tofogliflozin is mainly due to calorie loss with increased UGE. In addition, tofogliflozin also induces a metabolic shift from carbohydrate oxidation to fatty acid oxidation, which may lead to prevention of fat accumulation and inflammation in adipose tissue and liver. Tofogliflozin may have the potential to prevent obesity, hepatic steatosis and improve insulin resistance as well as hyperglycemia.

Dataset Information

Sodium glucose cotransporter 2 inhibitor dapagliflozin depressed adiposity and ameliorated hepatic steatosis in high-fat diet induced obese mice.

Publications

Sodium glucose cotransporter 2 inhibitor dapagliflozin depressed adiposity and ameliorated hepatic steatosis in high-fat diet induced obese mice.

Similar Datasets

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