Catapano, Angela Nutraceuticals administration in the modulation of the energy balance and body composition. [Tesi di dottorato]

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Abstract

Non-communicable diseases (NCDs), which include diabetes, cardio-metabolic diseases, cancer, autoimmune diseases and depression, cause disability and are responsible for approximately 72% of global deaths. The role of nutrition and lifestyle as determinants of NCDs has been extensively examined by the scientific community, recognizing low-grade chronic inflammation, mitochondrial dysfunction and oxidative stress as some of the causes of these diseases. It has been demonstrated that inadequate caloric intake, characterized by excessive energy intake associated with micronutrient deficiency, can influence inflammatory processes, acting on the pathophysiology of adipose tissue, but also compromising mitochondrial function in organs with greater metabolic capacity (liver, skeletal muscle and brain). The liver, in particular, plays a key role in regulating the body's metabolic and inflammatory homeostasis and, therefore, in the development of the metabolic alterations associated with obesity. Indeed, hepatic mitochondrial dysfunction can cause alterations in fat oxidation, free radical production and a significant increase in oxidative stress. The chronic inflammatory state and oxidative stress are largely modulated by nutritional choices, and therefore in recent years there has been a significant increase in the use of nutraceuticals and micronutrient supplements to correct nutritional deficiencies. The research aim was to evaluate the effects of a nutraceutical based on N-Dimethylglycine (DMG) and B vitamins on body composition and energy metabolism, modulation of inflammatory status and mitochondrial function in an animal model of diet-induced obesity. DMG is a glycine metabolism-related substance, similar to choline and betaine. It is found in small amounts in some foods such as meat, seeds and cereals, but is rapidly metabolised. DMG has been shown to reduce oxidative stress, improve immune responses and enhance athletic performance. On the other hand, B vitamins improve mitochondrial function. In order to evaluate the effects of DMG and B vitamins (DMG-B) administration on the metabolic and inflammatory profile of obese mice, animals were divided into two experimental groups: a control group fed a standard diet, and a High Fat Diet (HFD) group, fed a high-fat diet for 18 weeks. A subgroup of both the control and HFD groups were treated with DMG-B, intragastrically, for 4 weeks. Body weight and food intake were monitored daily. At the end of treatment, an analysis of energy expenditure, body composition and metabolic and inflammatory plasma parameters was performed. At liver level, mitochondrial function parameters, oxidative capacity, free radical production were evaluated and histological analyses were also carried out. The results showed that supplementation with the nutraceutical induced a significant reduction in body weight and total body lipids in animals fed HFD. In addition, the treatment resulted in an increase in energy metabolism and an improved ability to use fat as metabolic fuel. Biochemical analyses revealed a decrease in serum levels of triglycerides, cholesterol and transaminases, while blood values of pro-inflammatory markers, which were increased in HFD mice, were significantly reduced following treatment with the nutraceutical, as well as a reduction in leptin levels and an increase in adiponectin levels. The anti-inflammatory effect was also observed in the liver, confirming the efficacy of this product against steatosis induced by a hyperlipidic diet. Analysis of hepatic mitochondrial function revealed that mice fed HFD and treated with DMG-B showed increased fatty acid oxidation and reduced ROS production. The increase in fatty acid oxidation is due to increased oxidative capacity, but also to increased fatty acid transport. increased transport of fatty acids to the mitochondria. This explains the reduced serum levels of cholesterol and triglycerides, the decrease in body fat and the reduction in hepatic lipid content. Histological analyses have shown that treatment with DMG-B in obese mice improves hepatic steatosis and hepatocyte morphology, and reduces lipid deposits, improves antioxidant/detoxifying defences, and reduces hepatic peroxidation products. The analysis of the functional effects of DMG-B on energy expenditure and mitochondrial function in organs with a high metabolic rate is of considerable importance when considering the use of this nutraceutical for preventive and/or therapeutic purposes in NCD.

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