Potential Roles for DGB25 Adipose Thermogenesis

Overview

Potential roles for DGB25 adipose thermogenesis Jack Volpert1, Daniel Kramer2, Paul Cohen2 1 Riverdale Country School Bronx, NY 2Laboratory of Molecular Metabolism, Rockefeller University, NY, NY Obesity is a rapidly-escalating health crisis in the United States. Nearly one-third of Americans are obese, and another third are overweight. Obesity has considerable economic burdens; the U.S spent $147 billion on its direct medical costs in 2008 alone. To address an illness as complex as obesity, the Cohen Lab at Rockefeller studies the subtypes of fat cells (adipocytes): brown, white, and beige. Their goal is to develop therapeutic approaches toward stimulating healthy brown adipose tissue (BAT) and inducing healthy brown-like properties in white fat. BAT dissipates energy in the form of heat via non-shivering thermogenesis. Our project focuses on testing if the loss of Ucp1, a BAT-specific protein that converts chemical energy into heat by uncoupling mitochondrial respiration, will result in the compensatory upregulation of DGB25, an under-studied protein we hypothesize to also be associated with increased energy expenditure and weight loss. Both Ucp1 and DGB25 expression are most-enriched in BAT, suggesting they play significant parallel roles in thermogenesis and weight loss. We bred homozygous wildtype (functional UCP1) and homozygous mutant (non-functional UCP1) mice. We are currently acclimating the Ucp1 mutant and WT cohorts to a cold environment. Ucp1 mutant mice can’t survive acute cold exposure, so we lower the temperature incrementally, giving the Ucp1 mutant adipose time to upregulate alternative mechanisms of heat generation. In the Ucp1 mutant mice, we hypothesize an increase in DGB25 expression versus wildtype mice. This would suggest that DGB25 plays a role in thermogenesis. Our next experiment will involve knocking out DGB25 in mice and comparing the energy expenditure, body weights, and adipose health in the DGB25-normal and DGB25-deficient groups. A deeper understanding of the metabolic processes controlled by these proteins may lead to therapeutic benefits combating obesity and its associated metabolic diseases.

Competition history

• AJAS 2020 Category not listed

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