Showing papers by "Harvey J. Grill published in 2006"

Distributed neural control of energy balance: contributions from hindbrain and hypothalamus.

Abstract: Data are reviewed that support the hypothesis that the neural control of energy expenditure is distributed among several brain sites. This view contrasts with that expressed most commonly in literature, that a single site-the arcuate hypothalamic nucleus-receives and integrates signals of relevance to energy status assessment and engages the effector circuits that orchestrate responses that maintain energy balance. The data reviewed support a contribution from medullary neurons, including those of the nucleus of the solitary tract, in the integration of signals of relevance to energy balance and in the issuing of commands to local behavioral and autonomic effectors. Experimental evidence is discussed that supports the following specific conclusions: hindbrain neurons integrate oral and gastrointestinal signals and issue commands to local motor circuits that control meal size; leptin's effect on food intake may be mediated, in part, by a direct action on the hindbrain neurons that respond to gastric distention; deprivation signals, such as the fall in leptin level, affect gene expression outside of the hypothalamus with reductions in proglucagon and proopiomelanocortin message seen in nucleus of the solitary tract-rich tissue; and that hindbrain neurons contribute to the control of energy expenditure seen with food deprivation and increases in expenditure after cold exposure or starvation. Future work is needed to define how the nucleus of the solitary tract and arcuate nodes of the central energy balance control network interact to collectively, or separately, influence specific aspects of energy balance control in the intact brain.

Divergent regulation of proopiomelanocortin neurons by leptin in the nucleus of the solitary tract and in the arcuate hypothalamic nucleus.

Abstract: Proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) of the hypothalamus are activated by leptin and mediate part of leptin's central actions to influence energy balance. However, little is known about potential leptin signaling in POMC neurons located in the nucleus of the solitary tract (NTS), the only other known population of POMC neurons. Leptin-responsive neurons do exist in the NTS, but their neurochemical phenotype is largely unknown. The contribution of NTS POMC neurons versus ARC POMC neurons in leptin action is thus undetermined. We show here that in contrast to POMC neurons in the ARC, leptin does not stimulate phosphorylation of signal-transducer and activator of transcription 3 in NTS POMC neurons of POMC-EGFP reporter mice. In addition, leptin does not induce c-Fos expression in NTS POMC neurons unlike ARC POMC neurons. Fasting induces a fall in POMC mRNA in both the ARC and the NTS, but different from the ARC, the reduction in NTS POMC mRNA is not reversed by leptin. We conclude that POMC neurons in the NTS do not respond to leptin unlike ARC POMC neurons. POMC neurons in the hypothalamus may therefore mediate all of leptin's signaling via POMC-derived peptides in the central nervous system.

Overfeeding-induced weight gain suppresses plasma ghrelin levels in rats

Abstract: The elevation of plasma ghrelin associated with weight loss has been taken as evidence of a role for ghrelin in the adaptive response to body weight change. However, there has been no clear experimental evidence that circulating ghrelin is suppressed by weight gain. We investigate this issue using a model of involuntary (intra-gastric gavage) overfeeding-induced obesity. Rats were first maintained at normal body weight with 4 daily tube-feedings of liquid diet (2.11 kcal/ml), each delivered at a volume of 9 ml. Gavage volume was then increased to 13 ml/feeding for 2 weeks, during which rats gained 25% of their initial body weight. Fasting plasma ghrelin levels and the response to 9- and 13-ml intra-gastric load sizes were measured during the weight-stable and overfed conditions. We found that: 1) weight gain decreased circulating ghrelin levels; 2) this response could not be attributed to additional food in the gastrointestinal tract; 3) the ghrelin response to nutrient loads was diminished in the obese vs normal-weight conditions. Having discounted diet composition and differences in gastric contents at the time of blood sampling, the decrease in ghrelin levels with overfeeding can be unambiguously attributed to physiological correlates of weight gain.

Energy expenditure and body composition of chronically maintained decerebrate rats in the fed and fasted condition.

Abstract: The contribution of the caudal brainstem to adaptation to starvation was tested using chronically maintained decerebrate (CD) and neurologically intact controls All rats were gavage fed an amount of diet that maintained weight gain in controls CD rats were subjected to a two-stage surgery to produce a complete transection of the neuroaxis at the mesodiencephalic juncture One week later, the rats were housed in an indirect calorimeter, and 24 h energy expenditure was measured for 4 d One half of each of the CD and control groups was then starved for 48 h Fed CD rats maintained a lower body temperature (35 C), a similar energy expenditure per unit fat-free mass but an elevated respiratory quotient compared with controls They gained less weight, had 20% less lean tissue, and had 60% more fat than controls Circulating leptin, adiponectin, and insulin were elevated, glucose was normal, but testosterone was dramatically reduced Responses to starvation were similar in CD and controls; they reduced energy expenditure, decreased respiratory quotient, indicating lipid utilization, defended body temperature, mobilized fat, decreased serum leptin and insulin, and regulated plasma glucose These data clearly demonstrate that the isolated caudal brainstem is sufficient to mediate many aspects of the energetic response to starvation In intact animals, these responses may be refined by a contribution by more rostral brain areas or by communication between fore- and hind-brain In the absence of communication from the forebrain, the caudal brainstem is inadequate for maintenance of testosterone levels or lean tissue in fed or fasted animals