Discovering The Developmental Origins of Obesity

The Polish Academy of Sciences in Olsztyn, Poland

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Welcome Project

tn 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 (http://www.cdc.gov/HealthyYouth/obesity), 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.

Obesity biomarkers

Develop biomarkers that can identify individuals who have increased susceptibility to chronic disease as adults due to malnutrition and abnormal ambient temperatures experienced as newborn animals.

(Team Leaders: Andrzej Ciereszko PAS, Olsztyn; Indu Kheterpal PBRC, Baton Rouge LA, USA; Leslie P. Kozak PAS, Olsztyn)

Cytoskeleton & caveolae gene regulation during adipose tissue expansion

Identify signaling and transcription factors that coordinately regulate genes encoding proteins of the cytoskeleton and caveolae during adipose tissue expansion in 10 day-old mice.

(Team Leaders:  Leslie Kozak PAS, Olsztyn; Michael Salbaum Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA; Monika Kaczmarek PAS, Olsztyn and Barbara Gawronska-Kozak PAS, Olsztyn)

Microbiota and adipocyte expansion

Determine how the ambient temperature determines the effects of the microbiota of the lactating mother on the characteristics of adipose tissue expansion in strains of mice that vary in sensitivity to diet-induced obesity.

(Leader: Lidia Markiewicz)

Protein phosphatases and wBAT differentiation

Determine the role of the regulatory (inhibitory) 3B subunit of protein phosphatase1c on the differentiation of brown adipocytes in white fat depots during mal-nutrition.

(Team Leaders: Leslie P. Kozak, PAS Olsztyn and Robert Koza, PBRC, Baton Rouge, LA, USA)

WAT and wBAT stem cells/ preadipocytes

To exploit the effects of the nutritional and temperature environment on the emergence of white (WAT) and brown (wBAT) preadipocytes/stem cells within white fat depots during the early post-natal development.

(Leader: Barbara Gawronska-Kozak)