Article

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

ABSTRACT

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.

Full-text preview

Available from: onlinelibrary.wiley.com
  • Source
    • "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]). "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Jun 2011 · PLoS ONE
  • Source
    • "Hence, it is possible that signals involving energy homeostasis commonly affect the regulation of troponin T splicing. Research on mechanisms controlling body weight homeostasis has focused primarily on neuroendocrine regulation of food intake, satiety and energy storage depot size (Levin, 2006;McMinn et al., 2000;Morton et al., 2006;Schwartz et al., 2000). In concert with such mechanisms, our results suggest that there may be an important role for the skeletal musculature in maintaining proper body weight homeostasis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Do animals know at a physiological level how much they weigh, and, if so, do they make homeostatic adjustments in response to changes in body weight? Skeletal muscle is a likely tissue for such plasticity, as weight-bearing muscles receive mechanical feedback regarding body weight and consume ATP in order to generate forces sufficient to counteract gravity. Using rats, we examined how variation in body weight affected alternative splicing of fast skeletal muscle troponin T (Tnnt3), a component of the thin filament that regulates the actin-myosin interaction during contraction and modulates force output. In response to normal growth and experimental body weight increases, alternative splicing of Tnnt3 in rat gastrocnemius muscle was adjusted in a quantitative fashion. The response depended on weight per se, as externally attached loads had the same effect as an equal change in actual body weight. Examining the association between Tnnt3 alternative splicing and ATP consumption rate, we found that the Tnnt3 splice form profile had a significant association with nocturnal energy expenditure, independently of effects of weight. For a subset of the Tnnt3 splice forms, obese Zucker rats failed to make the same adjustments; that is, they did not show the same relationship between body weight and the relative abundance of five Tnnt3 β splice forms (i.e. Tnnt3 β2-β5 and β8), four of which showed significant effects on nocturnal energy expenditure in Sprague-Dawley rats. Heavier obese Zucker rats displayed certain splice form relative abundances (e.g. Tnnt3 β3) characteristic of much lighter, lean animals, resulting in a mismatch between body weight and muscle molecular composition. Consequently, we suggest that body weight-inappropriate skeletal muscle Tnnt3 expression in obesity is a candidate mechanism for muscle weakness and reduced mobility. Weight-dependent quantitative variation in Tnnt3 alternative splicing appears to be an evolutionarily conserved feature of skeletal muscle and provides a quantitative molecular marker to track how an animal perceives and responds to body weight.
    Full-text · Article · May 2011 · Journal of Experimental Biology
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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. ClinicalTrials.gov NCT00581074.
    Full-text · Article · Feb 2011 · Nutrition & Metabolism
Show more