Central Regulation of Energy Homeostasis Intelligent Design: How to Build the Perfect Survivor

Neurology Service, VA Medical Center, 385 Tremont Avenue, East Orange, NJ 07018-1095, USA.
Obesity (Impact Factor: 3.73). 09/2006; 14 Suppl 5(supplement 5):192S-196S. DOI: 10.1038/oby.2006.307
Source: PubMed


The perfect survivor must be able to eat and store as many calories as possible when food is readily available as a buffer against periods of scarcity. He must also reduce energy expenditure when food is scarce and efficiently and accurately restore lost adipose stores when food is again available. These processes are dependent on information relayed to a distributed central network of metabolic sensing neurons through hard-wired neural, metabolic, and hormonal signals from the periphery. These sensing neurons engage neuroendocrine, autonomic, and motor processes involved in arousal, motor activity, and the ingestion, absorption, assimilation, storage, and expenditure of calories. A raised threshold in these metabolic sensors for detecting inhibitory signals from increasing adipose stores allows continued intake of excess calories when they are readily available. Unfortunately, this mechanism for surviving periods of feast and famine predisposes the perfect survivor to become obese when highly palatable, energy dense foods are readily available at low energetic cost. It further assures that raised adipose stores are metabolically defended against attempts to lower them. Thus, effective treatment of obesity will only come with a better understanding of the physiological, metabolic, and neurochemical processes that ensure this defense of an elevated body weight.

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    • "It has now clearly been shown that nutrient sensing is a key factor in the regulation of energy homeostasis, especially that of glucose [1]. Indeed, daily variations in nutrient concentrations in both gut lumen and blood are detected by specific sensors located either in the gastrointestinal tract [2], [3] or in specialized central areas (mainly the hypothalamus or brainstem [4], [5]). "
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    ABSTRACT: Daily variations in lipid concentrations in both gut lumen and blood are detected by specific sensors located in the gastrointestinal tract and in specialized central areas. Deregulation of the lipid sensors could be partly involved in the dysfunction of glucose homeostasis. The study aimed at comparing the effect of Medialipid (ML) overload on insulin secretion and sensitivity when administered either through the intestine or the carotid artery in mice. An indwelling intragastric or intracarotid catheter was installed in mice and ML or an isocaloric solution was infused over 24 hours. Glucose and insulin tolerance and vagus nerve activity were assessed. Some mice were treated daily for one week with the anti-lipid peroxidation agent aminoguanidine prior to the infusions and tests. The intestinal but not the intracarotid infusion of ML led to glucose and insulin intolerance when compared with controls. The intestinal ML overload induced lipid accumulation and increased lipid peroxidation as assessed by increased malondialdehyde production within both jejunum and duodenum. These effects were associated with the concomitant deregulation of vagus nerve. Administration of aminoguanidine protected against the effects of lipid overload and normalized glucose homeostasis and vagus nerve activity. Lipid overload within the intestine led to deregulation of gastrointestinal lipid sensing that in turn impaired glucose homeostasis through changes in autonomic nervous system activity.
    PLoS ONE 06/2011; 6(6):e21184. DOI:10.1371/journal.pone.0021184 · 3.23 Impact Factor
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    • "Notably, the additional 8.5-16.5% reduction in energy intakes during the caloric restriction + preload phase was physiologically consistent with the 13.3% increase in the rate of weight loss during that phase. The compensation observed contrasts with some basic science models of energy balance utilizing the concept of negative adiposity feedback signaling to the brain [42-44] and data suggesting that obese individuals would defend adiposity and compensate for weight loss by increasing intakes of energy dense foods or total calories [42,44,45]. Nevertheless, our findings are consistent with the ability of individuals at lower BMI to respond to the energy content of an ingested preload [11]. "
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    ABSTRACT: Reducing dietary energy density has proven to be an effective strategy to reduce energy intakes and promote weight control. This effect appears most robust when a low energy dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of a preload. The purpose of the present study was to compare effects of a solid (grapefruit), liquid (grapefruit juice) and water preload consumed prior to breakfast, lunch and dinner in the context of caloric restriction. Eighty-five obese adults (BMI 30-39.9) were randomly assigned to (127 g) grapefruit (GF), grapefruit juice (GFJ) or water preload for 12 weeks after completing a 2-week caloric restriction phase. Preloads were matched for weight, calories, water content, and energy density. Weekly measures included blood pressure, weight, anthropometry and 24-hour dietary intakes. Resting energy expenditure, body composition, physical performance and cardiometabolic risk biomarkers were assessed. The total amount (grams) of food consumed did not change over time. Yet, after preloads were combined with caloric restriction, average dietary energy density and total energy intakes decreased by 20-29% from baseline values. Subjects experienced 7.1% weight loss overall, with significant decreases in percentage body, trunk, android and gynoid fat, as well as waist circumferences (-4.5 cm). However, differences were not statistically significant among groups. Nevertheless, the amount and direction of change in serum HDL-cholesterol levels in GF (+6.2%) and GFJ (+8.2%) preload groups was significantly greater than water preload group (-3.7%). These data indicate that incorporating consumption of a low energy dense dietary preload in a caloric restricted diet is a highly effective weight loss strategy. But, the form of the preload did not have differential effects on energy balance, weight loss or body composition. It is notable that subjects in GF and GFJ preload groups experienced significantly greater benefits in lipid profiles. NCT00581074.
    Nutrition & Metabolism 02/2011; 8(1):8. DOI:10.1186/1743-7075-8-8 · 3.26 Impact Factor
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    • "These brain nuclei not only communicate with each other, but they also receive and integrate neural and humoral information generated in the gut and other peripheral organs, which reflect the dynamic energy status and needs of the organism. Research from the past two decades suggests that while this system is well in balance to maintain energy homeostasis when an organism experiences daily moderate fluctuations in food intake, or even challenged by more severe circumstances such as occasional cycles of feast and famine, it is not designed to cope with prolonged periods of energy excess [1]. So, what exactly is happening in these networks, and in the periphery, when intake of highly palatable and energy–dense foods outweighs energy expenditure, resulting in obesity? "
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    ABSTRACT: Obesity develops despite a complex and seemingly well orchestrated network that controls eating, energy expenditure and ultimately body weight; many of the involved signals are derived from the gastrointestinal tract. It is assumed that this network as an entity aims at maintaining body weight and body adiposity at a relatively constant level, but the control mechanisms seem to fail at least if an individual is chronically exposed to an oversupply of food. This article summarizes recent findings about the role of amylin in the control of eating in lean and obese rodents. The article gives some short background information about the well investigated adiposity and satiating signals leptin and cholecystokinin, respectively; this will provide the framework to discuss aspects of amylin physiology and pathophysiology in the control of eating in leanness and obesity. This discussion also involves the mechanisms mediating amylin's eating inhibitory effect in the area postrema and the interactions between amylin and leptin. Further, we discuss the effect of high fat diets on amylin release and amylin action in lean and obese rats. The last part of this article raises the question whether amylin interacts with the reward system in the forebrain.
    Physiology & Behavior 02/2011; 105(1):129-37. DOI:10.1016/j.physbeh.2011.02.015 · 2.98 Impact Factor
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