Abstract
Accumulating evidence indicates that metabolic dysfunction with visceral obesity is a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM) and dyslipidemia, and ultimately severe cardiovascular and renal disease. Therefore, an effective anti-obesity treatment with a concomitant improvement in metabolic profile is important for the treatment of metabolic dysfunction with visceral obesity. Bofu-tsu-shosan (BOF) is one of oriental herbal medicine and is clinically available to treat obesity in Japan. Although BOF is a candidate as a novel therapeutic strategy to improve metabolic dysfunction with obesity, the mechanism of its beneficial effect is not fully elucidated. Here, we investigated mechanism of therapeutic effects of BOF on KKAy mice, a model of human metabolic disorders with obesity. Chronic treatment of KKAy mice with BOF persistently decreased food intake, body weight gain, low-density lipoprotein cholesterol and systolic blood pressure. In addition, both tissue weight and cell size of white adipose tissue (WAT) were decreased, with concomitant increases in the expression of adiponectin and peroxisome proliferator-activated receptors genes in WAT as well as the circulating adiponectin level by BOF treatment. Furthermore, gene expression of uncoupling protein-1, a thermogenesis factor, in brown adipose tissue and rectal temperature were both elevated by BOF. Intriguingly, plasma acylated-ghrelin, an active form of orexigenic hormone, and short-term food intake were significantly decreased by single bolus administration of BOF. These results indicate that BOF exerts a combinatorial favorable metabolic modulation including antihypertensive effect, at least partially, via its beneficial effect on adipose tissue function and its appetite-inhibitory property through suppression on the ghrelin system.
Highlights
Metabolic disorders with obesity have become a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM) and dyslipidemia, and life-threatening cardiovascular and renal diseases
We firstly examined the effect of BOF on food intake and body weight of KKAy mice
We showed that 1) BOF persistently decreased food intake and body weight gain; 2) BOF consistently decreased blood pressure without affecting heart rate; 3) BOF decreased white adipose tissue (WAT) weight and adipocyte hypertrophy, and ameliorated the adipocytokine dysregulation in WAT; 4) BOF increased Uncoupling Protein-1 (UCP-1) mRNA expression in brown adipose tissue (BAT) and the rectal temperature and 5) BOF decreased the short-term food intake and the plasma acylated-ghrelin level in KKAy mice, a model of human metabolic disorders with visceral obesity, T2DM, dyslipidemia and hypertension
Summary
Metabolic disorders with obesity have become a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM) and dyslipidemia, and life-threatening cardiovascular and renal diseases. Hypertension with obesity is closely associated with the development of systemic organ damage and arteriosclerosis together with T2DM and dyslipidemia, and increases the morbidity of cardiovascular and renal diseases [1,2,3,4]. An effective anti-obesity treatment with a concomitant improvement in metabolic profile is essential in hypertension with visceral obesity. Antiobesity drugs and bariatric surgery have only been able to help a limited number of severely obese people because of side effects and invasiveness of the procedure [7,8]
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