Each of the many factors by which lifestyle and environment influence energy balance interacts with specific sets of susceptibility genes, the variations of which determine the physiological impact of the particular factor. The initiation and maintenance of ingestive behavior is co-determined by metabolic and non-metabolic factors. Among the latter, environmental cues, as well as reward, cognitive, and emotional factors, play an important role, particularly in human food intake in the modern world.
DEFINITION OF ENERGETIC BALANCE
Energy balance is the difference between energy introduced with food and energy consumed. The energy need is divided into:
- Basal metabolism;
- Physical activity;
- Thermogenesis (aimed at maintaining body temperature and reduced by global warming)):
- Dynamic specific activity of foods;
- Thermogenesis not connected to physical exercise
- The energy need may be modified due to:
- Changes in performance of the respiratory chain;
- Changes in performance of physical work.
The necessity of taking food is regulated at the hypothalamic level in order to respond to hunger signals of hunger and satiety feelings, that are the result of integration at the level of different cortical signal from various sources and who have the task of regulating food intake, with a network of various chemical mediators and nervous. It was noted that in most mammalian species ( as well as in humans, if you live in the wild ), it tends to have a direct relationship between the amount of food consumed and the amount of work required to obtain. In civilized this simple report has been lost, but was still true at the man’s hunter and farmer.
Which is the role of global warming on obesity?
Monitoring of taking food.
HOMEOSTATIC REGULATION OF ENERGY BALANCE.
Future directions in weight control
Responsibility for controlling energy homeostasis is shared between several brain regions, as is evidenced in man by the effects on food intake of factors such as the sight and smell of food, the number and conviviality of eating companions, and the size and ultimate resting place of the restaurant bill (Hill & Peters, 1998).
The GI tract and the liver are involved in short-term regulation of feeding.Afferent signals travel in vagal nerve fibers from stretch receptors, and chemoreceptors activated by the presence of nutrients in the stomach and proximal small intestine are involved in meal termination. Nutrients arriving via the portal vein may also trigger vagal afferent signals from the liver. Glucose can modulate food intake by acting on glucose-responsive neurons in the CNS. Ketones appear to decrease appetite. In response to nutrient stimulation, the proximal intestine releases cholecystokinin (CCK), which reaches the liver via the portal vein and the CNS via the systemic circulation; CCK may act on CCK-A receptors at both sites to inhibit food intake. Endocrine L cells in the terminal small intestine (ileum) release glucagon-like peptide-1 (GLP-1), which inhibits feeding, most likely at a hepatic site or by inhibiting gastric emptying. The short-term signals by themselves do not produce sustained alterations in energy intake and body adiposity.
GLUCOSE: Hypoglycemia or inhibition of glucose metabolism with the glucose analog 2 deoxy-D-glucose increases food intake in animals and increases hunger sensations and food intake in humans ("Oomura and colleagues").
FAT (TRIGLYCERIDES, FATTY ACIDS, AND APOLIPOPROTEINS):
The intravenous infusion of lipid substrates such as Intralipid, along with heparin to release lipoprotein lipase and hydrolyze triglyceride to fatty acids and glycerol, decreases food intake in baboons. These data suggest that an increase of circulating lipids, in the absence of GI absorption, regulates feeding.
Like inhibition of glucose metabolism, inhibition of lipid metabolism increases expression of the orexigenic neuropeptide melanin concentrating hormone in the lateral hypothalamus. However, unlike glucoprivation, it does not increase expression of neuropeptide Y or agouti-related peptide in the arcuate nucleus , both of which are orexigens. Another lipid-related product potentially involved in the regulation of food intake is the apolipoprotein, ApoAIV. The production of Apo AIV in the intestine is stimulated by fat absorption, and administration of Apo AIV inhibits food intake. This apolipoprotein is also produced in the hypothalamus, and Apo AIV of central origin may also have a role in food intake regulation.
METABOLITES: Lactate, piruvate , and ketones inhibit feeding in animals. Postprandial circulating lactate concentrations are increased in proportion to the carbohydrate content of meals, and could therefore contribute to the short-term inhibition of food intake during carbohydrate consumption.
Long-term signals regulating food intake and energy homeostasis.
Insulin and leptin are the two most important long-term regulators of food intake and energy balance. Both insulin and leptin act in the CNS to inhibit food intake and to increase energy expenditure, most likely by activating the sympathetic nervous system.
The long-term signals interact with the short-term signals in the regulation of energy homeostasis and appear to set sensitivity to the satiety producing effects of short-term signal such as CCK.
Leptin, leptin receptors, and its downstream signaling pathways.
Leptin increases the consumption of fatty acids through oxidation in skeletal muscle. Moreover show that leptin activates an enzyme - protein kinase of 5 'monophosphate, or AMPK - in skeletal muscle. In cells, a fragile balance controls whether fatty acids are transported into mitochondria and are metabolized or stored in the cytoplasm as triglycerides. This balance is regulated mainly by malonil CoA, a fatty acid which is generated dall'acetil-CoA carboxylase (ACC). The malonil CoA inhibits the transport of fatty acids into mitochondria, thus preventing be metabolized . The AMPK phosphorylated ACC, inattivandolo. Through activation dell'AMPK in muscle, leptin inhibits the synthesis of malonil CoA and move the balance towards the oxidation of fatty acids and does not allow the storage of fat. These effects are similar to those visas in mice in which the genes that encode the ACC have been put out of use.
Obestatin derived from the same polypeptide precursor as ghrelin, but which rather suppresses food intake also appears to enhance learning and memory and, in addition, produces an anxiolytic effect as indicated by increased percentage of open arm entries in the elevated plus maze . There is also a considerable literature showing that leptin can modulate excitability of hippocampal neurons. Its dose-dependent differential effects on long-term potentiation and depression suggest that leptin can either facilitate or suppress memory functions .
Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R), present on pituitary cells secreting growth hormone. Ghrelin is most abundant in the stomach, and GHS-R is also present in the stomach and in other organs and tissues, suggesting effects beyond stimulation of growth hormone in the pituitary, and in particular in the regulation of gastrointestinal function. However, as yet ghrelin seems rather a signal by which the digestive system regulates functions other than the digestive process itself. The most important role of ghrelin appears to be stimulation of appetite and regulation of energy homeostasis, favouring adiposity, and thus contributing to obesity. As recently suggested, ghrelin may therefore be called the "saginary" (fattening) peptide. The gut hormone ghrelin has been shown to directly act on hippocampal neurons and induce formation of new synapses in the CA1 region. The ghrelin-induced changes in synaptic density were correlated with enhanced spatial learning. Ghrelin-deficient mice exhibited impaired spatial learning that was corrected by ghrelin administration . These findings are consistent with the idea that ghrelin is involved in the appetitive phase of ingestive behavior when it is important to find food in the environment. It is plausible that the ghrelin-induced changes in hippocampal function facilitate the recall of stored representations of prior experience with food. This is indicated by human subjects reporting a vivid, plastic image of their preferred meal upon intravenous ghrelin infusion.
NON HOMEOSTATIC REGULATION OF ENERGY BALANCE.
Memonic representations of experience with food.
Representations of experience with foods are generated in the orbit frontal and insular cortex. Reward from palatable food is processed by a complex neural system that includes the nucleus accumbens and ventral pallidum in the ventral striatum, the ventral tegmental area (VTA) located in the midbrain and projecting through the mesolimbic dopamine system back to the nucleus accumbens, the prefrontal cortex, the hippocampus, and amygdala. Nutritionally relevant hormones can modulate activity of the mesolimbic dopamine system.Leptin and insulin can act directly on mesolimbic dopamine neurons to modulate ‘wanting’ for food. Orexin neurons, known to be activated by hypoglycemia, may augment food intake by their stimulation of dopamine neurons in the VTA . Orexin, together with galanin, enkephalin,and dynorphin, may also provide a paradoxical positive feedback between circulatin glipid sand further stimulation of food intake. In addition, orexin projections to the olfactory bulb appear to modulate the sensitivity of peripheral olfactory processing. While leptin decreases, orexin increases the ability to smell potential food.
Homeostitic and non-homeostatic pathways
Neuroendocrinal control of appetite
open question: I assume that the real sensor of energy production (ATP) is cAMP that is able to diffuse out of the working cells and to reduce appetite
Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1alpha. 2006 Fulltext
The central (i.c.v.) administration of C75 (a potent Fatty Acid Synthase inhibitor) rapidly (≤2 h) increased the malonyl-CoA level in the hypothalamus, which was accompanied by the rapid up-regulation of fatty acid oxidation in skeletal muscle