Kozak_Les_BLeslie P. Kozak, PhD

Faculty Scientist III


BS: St. John Fisher College, Rochester, NY
PhD: Department of Chemistry, University of Notre Dame

Discovering the developmental origins of obesity

The energy balance equation explains with a simple formula the idea that energy intake must be in balance with energy expenditure to maintain a stable body weight. Because the energy balance equation is based upon the fundamental laws of thermodynamics, we know with scientific certainty that a life style and/or genetic constitution that leads to a positive energy balance, which occurs when energy intake is greater than energy expenditure, will lead to obesity.  However, we do not know the structural-functional properties of our genetic constitution nor the interactions between our genes and environmental conditions that will lead to a positive energy balance.  The realization of our genetic potentiality begins in the germ cells of our parents and continues through development in utero and during the post-natal suckling period.  The goal of this research project is to determine the genetic and environmental conditions that affect one critical system of energy balance, that is, the adipose system.

Birth instantly presents the newborn mammal with 2 life determining challenges, acquisition of caloric energy by nursing and the maintenance of body temperature. Adipose tissue plays a vital and necessary role in both of these physiological processes. How these challenges are met has life-long consequences on energy balance in adults.  As powerfully described in an epidemiological study of adult men who were at critical stages of fetal or post-natal development during the Dutch Famine in the winter of 1945, mal-nutrition during  early development can either stimulate or suppress susceptibility to obesity in adults. Accordingly, a major challenge lies in determining the molecular and cellular process affected by the nutritional environment during early development that will determine the capacity for adipose tissue expansion.

Acquisition and management of caloric energy and maintenance of body temperature depend on white and brown adipocytes.  White adipocytes have the biochemical mechanisms to store fat in lipid vesciles  and then release it to the system when energy stores are low, whereas the reciprocal function of brown fat is to produce heat to maintain body temperature. Do the interconnected, opposing functions of brown and white adipocytes, symbolized by the ying-yang motif, have long term effects on energy balance of an individual?  Accordingly, the Kozak laboratory seeks to determine how changes in energy balance as a consequence of variation in environmental temperature and diet during early post-natal development establishes the cellular balance between white and brown adipocytes.

Kozak LP, Birkenmeier EH. Mouse sn-glycerol-3-phosphate dehydrogenase: molecular cloning and genetic mapping of a cDNA sequence. Proc Natl Acad Sci USA 80:3020-4.

Boyer B, Kozak LP. 1991. The mitochondrial uncoupling protein gene in brown fat: Correlation between DNase 1 hypersensitivity and expression in transgenic mice. Mol Cell Biol 11:4147-56.

Kozak LP, Kozak UC, Clarke GT. 1991. Abnormal brown and white fat development in transgenic mice over-expressing glycerol-3-phosphate dehydrogenase. Genes Dev 5:2256-64.

Kopecky J, Clarke G, Enerback S, Spiegelman B, Kozak LP. 1995. Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. J Clin Invest 96:2914-2923.

Enerback S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper M-E, Kozak LP. 1997. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387:90-94.

Ackerman SL, Kozak LP, Przyborski SA, Rund LA, Boyer BB, Knowles BB. 1997. The mouse rostral cerebellar malformation gene encodes an UNC-5 like protein. Nature 386:838-842.

Guerra C, Koza R, Yamashita H, King KW, Kozak LP. 1998. Emergence of brown adipocytes in white fat is under genetic control. Effects on body weight and adiposity. J Clin Invest 102:412-420.

Liu X, Rossmeisl M, McClaine J, Riachi M, Harper M-E and Kozak LP. 2003. Paradoxical resistance to diet-induced obesity in UCP1-deficient mice. Clin. Invest. 111:399-407.

Kozak, LP. 2010. Brown Fat and the myth of diet-induced thermogenesis. Cell Metab 11:263-267.

Jaroslawska J, Chabowska-Kita A, Kaczmarek M and Kozak LP 2015 Npvf: Hypothalamic biomarker of ambient temperature independent of nutritional status. PLOS Genetic 1/23

Academic Appointments

  • Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Olsztyn, Poland
  • Maine Medical Center Research Institute, Scarborough, Maine

Professional Memberships

  • American Society for Biochemistry and Molecular Biology
  • North American Association for the Study of Obesity