Dataset Information

Daisaikoto Prevents Post-dieting Weight Regain by Reversing Dysbiosis and Reducing Serum Corticosterone in Mice.

ABSTRACT: Weight loss is often temporary and is generally followed by recurrent weight gain and a relapse of metabolic complications, whose severity may be even greater upon recurrence. Preventing recurrent obesity, understanding the control of the energy balance subsequent to weight loss, and reversing the predisposition to obesity are critical factors that warrant an in-depth study. Several Kampo medicines, including daisaikoto, have traditionally been used to manage obesity, but their mechanisms of action are not well studied and their effects on weight regain are unknown. Here, we investigated the therapeutic potential and mechanism of action of daisaikoto in a mouse model of recurrent obesity. The mouse model was established by feeding mice a high-fat diet, followed by a normal chow, and a second course of the high-fat diet. Daisaikoto inhibited not only obesity and regaining of weight post-dieting, but also dysbiosis, thereby overcoming the predisposition to obesity. Furthermore, we found that recurrent obesity or long-term consumption of the high-fat diet elevated serum glucose, insulin, and corticosterone levels, and that daisaikoto lowered serum cholesterol and free fatty acid levels. These results are consistent with the hypothesis that this medication may inhibit lipid absorption by inhibiting pancreatic lipase. However, daisaikoto had no effect on the body weight of lean mice fed a normal chow, suggesting that although this medicine prevents lipid absorption, it does not cause excessive weight loss. In conclusion, our results elucidate the mechanisms underlying daisaikoto activity, and suggest that it may serve as a safe and effective anti-obesity drug.

SUBMITTER: Kawashima T

PROVIDER: S-EPMC6923278 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Daisaikoto Prevents Post-dieting Weight Regain by Reversing Dysbiosis and Reducing Serum Corticosterone in Mice.

Kawashima Takanori T Ogata Misaki M Fujita Nina N Takahashi Ryuji R

Frontiers in physiology 20191213

Weight loss is often temporary and is generally followed by recurrent weight gain and a relapse of metabolic complications, whose severity may be even greater upon recurrence. Preventing recurrent obesity, understanding the control of the energy balance subsequent to weight loss, and reversing the predisposition to obesity are critical factors that warrant an in-depth study. Several Kampo medicines, including daisaikoto, have traditionally been used to manage obesity, but their mechanisms of act ...[more]

PMID: 31920693

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Project description:Obesity is a major global health problem and predisposes individuals to several comorbidities that can affect life expectancy. Interventions based on lifestyle modification (for example, improved diet and exercise) are integral components in the management of obesity. However, although weight loss can be achieved through dietary restriction and/or increased physical activity, over the long term many individuals regain weight. The aim of this article is to review the research into the processes and mechanisms that underpin weight regain after weight loss and comment on future strategies to address them. Maintenance of body weight is regulated by the interaction of a number of processes, encompassing homoeostatic, environmental and behavioural factors. In homoeostatic regulation, the hypothalamus has a central role in integrating signals regarding food intake, energy balance and body weight, while an 'obesogenic' environment and behavioural patterns exert effects on the amount and type of food intake and physical activity. The roles of other environmental factors are also now being considered, including sleep debt and iatrogenic effects of medications, many of which warrant further investigation. Unfortunately, physiological adaptations to weight loss favour weight regain. These changes include perturbations in the levels of circulating appetite-related hormones and energy homoeostasis, in addition to alterations in nutrient metabolism and subjective appetite. To maintain weight loss, individuals must adhere to behaviours that counteract physiological adaptations and other factors favouring weight regain. It is difficult to overcome physiology with behaviour. Weight loss medications and surgery change the physiology of body weight regulation and are the best chance for long-term success. An increased understanding of the physiology of weight loss and regain will underpin the development of future strategies to support overweight and obese individuals in their efforts to achieve and maintain weight loss.

Project description:Increased glucocorticoid (GC) levels act as a master contributor to central obesity in estrogen-depleted females; however, what factors cause their increased GC production is unclear. Given (1) liver fibroblast growth factor 21 (FGF21) and GCs regulate each other's production in a feed-forward loop, and (2) circulating FGF21 and GCs are parallelly increased in menopausal women and ovariectomized mice, we thus hypothesized that elevation of hepatic FGF21 secretion causes increased GGs production in estrogen-depleted females. Using the ovariectomized mice as a model for menopausal women, we found that ovariectomy (OVX) increased circulating corticosterone levels, which in turn increased visceral adipose Hsd11b1 expression, thus causing visceral obesity in females. In contrast, liver-specific FGF21 knockout (FGF21 LKO) completely reversed OVX-induced high GCs and high visceral adipose Hsd11b1 expression, thus abrogating OVX-induced obesity in females. Even though FGF21 LKO failed to rescue OVX-induced dyslipidemia, hepatic steatosis, and insulin resistance. What's worse, FGF21 LKO even further exacerbated whole-body glucose metabolic dysfunction as evidenced by more impaired glucose and pyruvate tolerance and worsened insulin resistance. Mechanically, we found that FGF21 LKO reduced circulating insulin levels, thus causing the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes in OVX mice. Collectively, our results suggest that liver FGF21 plays an essential role in mediating OVX-induced central obesity by promoting GC production. However, lack of liver FGF21 signaling reduces insulin production and in turn causes the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes, highlighting a detrimental role for hepatic FGF21 signals in mediating the development of central obesity but a beneficial role in preventing metabolic abnormality from further exacerbation in estrogen-depleted females.

Dataset Information

Daisaikoto Prevents Post-dieting Weight Regain by Reversing Dysbiosis and Reducing Serum Corticosterone in Mice.

Publications

Daisaikoto Prevents Post-dieting Weight Regain by Reversing Dysbiosis and Reducing Serum Corticosterone in Mice.

Similar Datasets

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