Discovering The Developmental Origins of Obesity

The Polish Academy of Sciences in Olsztyn, Poland


Welcome Project

tn wBAT miceDuring the nursing period of post-natal development two independent developmental processes determine the state of adipose tissue, one is a hard-wired developmental process known as adipogenesis, the other is a process dependent upon two variable environmental conditions, one is the nutritional state and the other is the ambient temperature.  Variation in nutrition and temperature continually determine the state of energy balance. Using a mouse model in which the caloric intake of the dam is manipulated during post-natal development, we have established that the nutritional environment during the nursing period determines the capacity for adipose tissue development by 10 days of age. This capacity is a genetically independent fixed phenotypic trait that maintains its effect on the physiology of an individual into adulthood. Knowing how strongly the ambient temperature affects adiposity in adult mice, we are now exploring the consequences of a low ambient temperature on the early development of both brown (BAT) and white (WAT) adipose tissues.  The clinical significance of temperature is obvious from the epidemic of childhood obesity in Southern USA (, the burst in childhood obesity in Europe in general, but especially in the southern/Mediterranean regions  (International Obesity Task Force, London 2002 ), and the recent realization that adult humans have depots of brown adipose tissue. This has led us to the present hypothesis: An imbalance in nutrition and chronic high ambient temperatures during early development are major environmental determinants of childhood obesity.

UCP-1 and alternative thermogenesis

tn cold adaptative thermogenesisMice in which the Ucp1 gene has been inactivated by genetic engineering has established the importance of the UCP1 protein in maintaining body temperature by the production of heat. While one is tempted to say that this specific genetic experiment has established that UCP1 is necessary (and maybe sufficient) for the production of heat to protect body temperature; there are exceptional phenotypes reminding us that the physiological dynamics of heat production are much more varied and interesting than simply adrenergic activation of brown fat thermogenesis. The appearance of novel thermodynamic phenotypes in fact owe their discovery to the targeted inactiviation of Ucp1 by homologous recombination.  What are some of these thermogenic phenotypes that require resolutions.