The hypothalamus plays a major role in the control of energy balance via the coordination of several neuropeptides and their receptors. We used a unique polygenic animal model of obesity, Psammomys obesus, and performed differential display polymerase chain reaction on hypothalamic mRNA samples to identify novel genes involved in obesity. In this study, we describe a novel gene that encodes a small protein we have termed "beacon." Beacon mRNA gene expression in the hypothalamus was positively correlated with percentage of body fat. Intracerebroventricular infusion of beacon resulted in a dose-dependent increase in food intake and body weight and an increase in hypothalamic expression of neuropeptide Y (NPY). Simultaneous infusion of beacon and NPY significantly potentiated the orexigenic response and resulted in rapid body weight gain. These data suggest a role for beacon in the regulation of energy balance and body weight homeostasis that may be mediated, at least in part, through the NPY pathway.
Psammomys obesus (the Israeli sand rat) has been
well studied as an animal model of Type 2 diabetes.
However, obesity phenotypes in these animals have
not been fully characterized. We analyzed phenotypic
data including body weight, percentage body
fat, blood glucose and plasma insulin concentration
for over 600 animals from the Psammomys obesus
colony at Deakin University to investigate the
relationships between body fat, body weight and
Type 2 diabetes using regression analysis and
general linear modelling. The body weight distribution
in Psammomys obesus approximates a normal
distribution and closely resembles that observed in
human populations. Animals above the 75th percentile
for body weight had increased body fat
content and a greater risk of developing diabetes.
Increased visceral fat content .was also associated
with elevated blood glucose and plasma insulin
concentrations in these animals. A familial effect
was also demonstrated in Psammomys obesus, and
accounted for 51% of the variation in body weight,
and 23–26% of the variation in blood glucose and
plasma insulin concentrations in these animals.
Psammomys obesus represents an excellent animal
model of.obesity and Type 2 diabetes that exhibits a
phenotypic pattern closely resembling that observed
in human population studies. The obesity described
in these animals was familial in nature and was
significantly associated with Type 2 diabetes.
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