Obesity is caused by an energy imbalance, where energy intake from eating food exceeds energy expended by physical exertion and metabolism. This proposal will provide a fundamental advance in our understanding of how the brain communicates with fat to control energy expenditure and body weight.
Reproduction is dependent upon the secretion of gonadotropin releasing hormone (GnRH) from the brain, that stimulates gonadotropin synthesis and release from the pituitary gland. In turn, GnRH and gonadotropin secretion is controlled by feedback effects of gonadal steroids such as estrogen. Various neural systems regulate GnRH cells. Kisspeptin is a recently discovered neuropeptide that appears to play a major role in the regulation of GnRH cells. Because it is newly recognized, the significance ....Reproduction is dependent upon the secretion of gonadotropin releasing hormone (GnRH) from the brain, that stimulates gonadotropin synthesis and release from the pituitary gland. In turn, GnRH and gonadotropin secretion is controlled by feedback effects of gonadal steroids such as estrogen. Various neural systems regulate GnRH cells. Kisspeptin is a recently discovered neuropeptide that appears to play a major role in the regulation of GnRH cells. Because it is newly recognized, the significance of kisspeptin and the relevant receptor, GPR54, is not well defined. This project aims to use our unique combination of abilities to determine the significance of kisspeptin in the regulation of GnRH and gonadotropin secretion. We will study both sheep and monkey brains, measuring gene expression for kisspeptin and GPR54 in a range of physiological states and we will determine how kisspeptin acts on GnRH cells. We will determine whether kisspeptin plays a role in the feedback effects to GnRH cells. Effects on the pituitary gland will also be studied. We will use sheep models to measure kisspeptin effects on GnRH secretion, because this cannot be done in the monkey or the rodent. We will examine the function of kisspeptin and GPR54 in relation to puberty. We will also use a model of puberty (seasonal breeding in the sheep) to determine whether activation and quiescence of the reproductive system is related to the function of kisspeptin and GPR54. This work will define the role of kisspeptin in the regulation of reproduction.Read moreRead less
While it is clear that carrying excess body weight can jeopardize your health, and that losing excess weight is good for you, attaining and maintaining a healthy body weight remains an elusive goal for more than 60 % of Australian adults. There are many barriers that make permanent weight loss difficult. One of the main biological barriers to weight loss is that humans aren t designed to diet. Instead, we vehemently conserve body fat whenever food is scarce. This leads to a Famine Reaction that ....While it is clear that carrying excess body weight can jeopardize your health, and that losing excess weight is good for you, attaining and maintaining a healthy body weight remains an elusive goal for more than 60 % of Australian adults. There are many barriers that make permanent weight loss difficult. One of the main biological barriers to weight loss is that humans aren t designed to diet. Instead, we vehemently conserve body fat whenever food is scarce. This leads to a Famine Reaction that contributes to nagging hunger, lethargy, loss of libido, reduced metabolic rate, plateaus, and rebound weight gain in response to weight loss programs of any kind. In a new 3-year project funded by the National Health and Medical Research Council of Australia, molecular scientists Dr Amanda Sainsbury-Salis and Associate Professor Herbert Herzog from the Garvan Institute endeavor to get to the root of the problem. Using cutting-edge molecular, genetic, and metabolic technology, Sainsbury-Salis and Herzog aim to identify the main culprits for the Famine Reaction. They hypothesize that the natural brain molecules neuropeptide Y and the endogenous morphine-like peptide dynorphin act together as major instigators of the Famine Reaction. Therefore they will determine whether mice that are deficient in these molecules can lose more weight in response to dietary restriction than normal mice. Moreover, they will determine whether dual deficiency of neuropeptide Y and dynorphin can not only reduce the voracious appetite that occurs during caloric restriction (eg: dieting), but whether it can also speed up metabolism and promote the loss of body fat. If their hypothesis proves correct, then it s likely that novel pharmaceutical agents that block the effects of neuropeptide Y and dynorphin could dramatically increase the do-ability and long-term effectiveness of lifestyle changes for permanent weight loss.Read moreRead less