Diet-induced hypothalamic dysfunction and metabolic disease, and the therapeutic potential of polyphenols

Abstract

Background The prevalence of obesity and metabolic diseases continues to rise globally. The increased consumption of unhealthy energy-rich diets that are high in fat and sugars results in oxidative stress and inflammation leading to hypothalamic dysfunction, which has been linked with these diseases. Conversely, diets rich in polyphenols, which are phytochemicals known for their antioxidant and anti-inflammatory properties, are associated with a reduced risk for developing metabolic diseases. Scope of review This review provides an overview of the effects of polyphenols against diet-induced hypothalamic dysfunction with respect to neural inflammation and mitochondrial dysfunction. Results show that polyphenols ameliorate oxidative stress and inflammation within the hypothalamus, thereby improving leptin signaling and mitochondrial biogenesis. Furthermore, they protect against neurodegeneration by decreasing the production of reactive oxygen species and enhancing natural antioxidant defense systems. Major conclusions The potential of polyphenols as nutraceuticals against hypothalamic inflammation, mitochondrial dysfunction, and neurodegeneration could hold tremendous value. With hypothalamic inflammation increasing naturally with age, the potential to modulate these processes in order to extend longevity is exciting and warrants exploration. The continued escalation of mental health disorders, which are characterized by heightened neuronal inflammation, necessitates the furthered investigation into polyphenol therapeutic usage in this regard.

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

“…Therefore, in both the central and peripheral tissues, uncontrolled or chronic inflammation accompanies IR ( Saltiel and Olefsky, 2017 ). Interestingly, inflammation also underlies hypothalamic dysfunction in obesity ( Samodien et al, 2019 ). New evidence indicates that it is the inflammation and stress of the endoplasmic reticulum that are critical pathogenetic events in the central and peripheral IR in metabolic disorders ( Arruda et al, 2011 ).…”

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…They are widely distributed in fruits, vegetables, and highly present in foods like legumes, cocoa, some cereals as well as in some beverages, such as tea, coffee and wine [ 29 ]. Polyphenols are not essential nutrients for humans but research in nutrition, including epidemiological studies, randomized controlled trials, in vivo and in vitro assays with animal models and cell lines, has shown that long-term and acute intakes can have beneficial effects on weight management and chronic diseases such as CVD, obesity, type 2 diabetes, the onset and development of some cancers and cognitive function [ 13 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ].…”

“…On the other side, diet-induced hypothalamic inflammation and mitochondrial dysfunction result in the onset and development of obesity and related metabolic diseases. It has been shown that, in rats, high fat diet (HFD) induces metabolic inflammation in the central nervous system (CNS), particularity in the hypothalamus [ 13 ].…”

Hypothalamic Inflammation as a Potential Pathophysiologic Basis for the Heterogeneity of Clinical, Hormonal, and Metabolic Presentation in PCOS

“…Caloric restriction may also represent another efficient approach [ 106 ]. Several studies also support the role of diets rich in polyphenols, to modulate the inflammatory response and oxidative stress in the hypothalamus [ 107 ]. Moreover, exercise has a beneficial effect in the reduction of body weight alone but also in tempering the installed hypothalamic inflammation by decreasing microglia activation and by improving glucose intolerance [ 108 ].…”