Fasting-mimicking diet prevents high-fat diet effect on cardiometabolic risk and lifespan

Abstract

Diet-induced obesity is a major risk factor for metabolic syndrome, diabetes and cardiovascular disease. Here, we show that a 5-d fasting-mimicking diet (FMD), administered every 4 weeks for a period of 2 years, ameliorates the detrimental changes caused by consumption of a high-fat, highcalorie diet (HFCD) in female mice. We demonstrate that monthly FMD cycles inhibit HFCDmediated obesity by reducing the accumulation of visceral and subcutaneous fat without causing loss of lean body mass. FMD cycles increase cardiac vascularity and function and resistance to cardiotoxins, prevent HFCD-dependent hyperglycaemia, hypercholesterolaemia and hyperleptinaemia and ameliorate impaired glucose and insulin tolerance. The effect of monthly FMD cycles on gene expression associated with mitochondrial metabolism and biogenesis in adipocytes and the sustained ketogenesis in HFCD-fed mice indicate a role for fat cell reprogramming in obesity prevention. These effects of an FMD on adiposity and cardiac ageing could explain the protection from HFCD-dependent early mortality.

Nutrition, longevity and disease: From molecular mechanisms to interventions

“…FMD also promotes a gene expression profile in the pancreas similar to that observed during embryonic development, leading to the reversal of the depletion in functional beta cells and reduced insulin production in a type 1 diabetes model (Cheng et al, 2017). FMD cycles applied for 5 days once a month to mice on a high-fat/calorie diet, lower body fat, improve cardiac function, lower cholesterol, and restore lifespan to the levels observed in mice on a standard diet (Mishra et al, 2021). Additional health benefits of FMD cycles lasting 4 days include extended longevity, reduced tumor incidence, and delayed cognitive decline, even when started at middle age (Brandhorst et al, 2015).…”

“…Excess glucose is directed to the synthesis of triglycerides in the liver, which are transported to adipose tissue and muscle by VLDL. Genetics influence the response to dietary interventions, but in general a diet providing high levels of saturated fats and sugars appears to be effective in generating obesity, insulin resistance, high cholesterol, and a shortened lifespan (Mishra et al, 2021;Wali et al, 2020). In mice and rats, the calories from fat intake that promote obesity and insulin resistance is typically in the 40%-60% range, but these high-fat diets in general also contain high levels of sugars (Wali et al, 2020).…”

Dietary regulation in health and disease

“… 196 In obese models induced by a fat-rich diet, a 5-day fasting-mimicking diet (FMD) is able to promote visceral and subcutaneous fat loss and protect against obesity-impaired cardiac vascularity and function. 260 Similar to CR, IF retards hypertension pathogenesis in rats through alteration of the metabatic profile in the caecum and plasma and the composition of the gut microbiota. 261 Considering food composition, high fibre consumption is discovered to elevate the richness of SCFA-generated microbial communities to include Bacteroides acidifaciens.…”

Astilbin fromSmilax glabraRoxb. alleviates high-fat diet-induced metabolic dysfunction

“…The unreasonable dietary structure of the population, the continuous increase in the ratio of lipid energy supply, and a sedentary lifestyle are the direct causes of individual overweight and obesity. 2,4 They are important risk factors for chronic diseases, such as diabetes, nonalcoholic fatty liver, and a variety of cancers. 5,6 Multiple human studies found an association between food patterns characterized by high-fat diet (HFD) choices and the prevalence of obesity.…”