br Energy absorption and metabolic

Energy MK0752 and metabolic homeostasis Because of an increase in the number of diseases caused by overnutrition, several studies have focused on the relationship between energy intake and balanced metabolism and health. After the absorption of energy substances such as glucose, the body first activates the secretion of insulin, then inhibits glucagon activity and gluconeogenesis, and finally promotes glycogenesis. In case of an emergency, the situation is reversed, i.e., the body first activates glucagon and induces insulin resistance to ensure that energy storage and consumption are strictly controlled to balance the metabolism. Diseases occur once the metabolic balance is out of control.
Overnutrition and metabolic syndrome
Nutrition and lifespan Nutrition, especially sensing and absorption of energy substances, not only plays an important role in the intensity of life activities and storage of energy substances but also controls aging and lifespan. More activity and rapid growth result in shorter life expectancy, and less activity and slower growth result in longer life expectancy. Members of SIRT protein family may play an important role in prolonging lifespan in nematodes. Although results of previous studies are controversial, physiological functions and mechanisms of these proteins have garnered interest [100]. Initially, Sir2 was recognized as an extra gene copy of non-expressible yeast mating type information gene [101]. Later, it was found that the Sir2 protein encoded by this gene has histone deacetylation activity that is dependent on NAD+[102]. During the process of executing activity, in fact, NAD+ was degraded into nicotinamide and 1-O-acetyl-ADP-ribose [103]. Because NAD+/NADH serve as a cofactor in various metabolic reactions, Sir2 is speculated to perform a sensing role in cell metabolism [104]. This gene has seven homologous genes (SirT1–SirT7) in animals [105]. Proteins encoded by all these homologous genes contain a conserved domain that forms their catalytic core; however, all these proteins show different subcellular localization [106]. Metabolic pathway is considered to be a network. From a traditional view, the activities of enzymes involved in central metabolic pathways can be regulated, but the expression of these enzymes cannot be regulated.] However, many recent studies on various enzymes involved in the central metabolic pathway indicate that expression of these genes is regulated by post-translational modification of nucleosome histones. Covalent modification of histones involves phosphorylation, acetylation, and methylation [107]. HATs [108] are special modifying enzymes that catalytically transfer active acetyl group from acetyl-CoA to amino group of lysine side chain in histones [109]. Molecules involved in nucleosome histone modifications, such as ATP, acetyl-CoA, and NAD+/NADH, are closely associated with energy metabolism. Thus, the modification status of histones after translation in the cytoplasm is an indicator of energy-supplying status of the body. Brian et al. [110] applied quantitative mass spectrometry to analyze acetylation kinetics and stoichiometric change in yeast. Their findings indicate an obvious difference in acetylation during growth and dormant periods and dependency on acetyl-CoA concentration. Concentration of acetyl-CoA in the mitochondria is significantly higher than that in the cytoplasm. These results suggest that histone acetylation reflects catabolism of glucose or fat and body\'s energy-supplying status through oxidative phosphorylation. Thus, more energy supply in the body can lead to higher accumulation of energy and exuberant energy metabolism, leading to a shorter lifespan. In contrast, energy restriction, appropriate starvation, or low calorie intake can reduce catabolism and oxidative phosphorylation, thus prolonging the lifespan. Its signaling pathways and logical relationships can be summarized as follows: High-energy nutrients (carbohydrates and fats) are digested and absorbed in the intestine. These nutrients are quantitatively sensed by GPCRs and then absorbed, stored, mobilized, and decomposed for energy supply by hormones secreted by the nerve and intestine–brain endocrine systems. More active catabolism and oxidative phosphorylation for energy supply result in shorter life expectancy and vice versa. Overall regulation of sugar catabolism depends on lactic acid cycle, and the overall regulation of fat catabolism depends on the circulation of ketone bodies. Both the metabolic pathways show crosstalk at acetyl-CoA, ATP, and NAD+/NADH. These important compounds in turn regulate catabolism and metabolic homeostasis through post-translational enzymatic modification of histones and enzyme regulation at multiple levels.