Adipose Metabolic Control in the Gerhart-Hines Group

The Gerhart-Hines group investigates the regulation of adipose metabolism in the context of systemic energy homeostasis.

Research focus

The overarching goal of the Gerhart-Hines group is to uncover how environmental and circadian cues govern adipose biology and coordinate organismal energy metabolism.

Specifically, we focus on which cell surface receptors and intracellular enzymes and transporters shape adipose tissue bioenergetics. We hope to leverage our discoveries towards the development of next generation treatment strategies for metabolic diseases, including obesity, diabetes, and NASH/NAFLD. By using a combination of omics platforms, state-of-the-art in vivo physiological phenotyping, and pharmacological engineering, we believe we are ideally poised to uncover key paradigms of adipose biological control and maximally exploit therapeutic potential.

Main findings

“NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity”
This work was published in Molecular Metabolism in 2018. One of the characteristics features of adipose tissue is its capacity to store energy and expand in size when dietary calories are plentiful and to reduce in size and provide energy when calories are scarce. However, little is known about the cellular mechanisms mediating this plasticity. In this study, we show for the first time that the NAD+ biosynthetic enzyme, NAMPT, is an essential regulator of adipose expansion. Genetic depletion of NAMPT in adipose tissue completely prevents mice from gaining weight and becoming obese even on a diet rich in fat.

“Cardiolipin Synthesis Governs Systemic Energy Homeostasis through Thermogenic Fat Mitochondria” 
This work was published in Cell Metabolism in 2018. Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. In this study, we found that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Additionally, we unexpectedly discovered a novel role for cardiolipin in mediating communication from the mitochondria to the nucleus as an indicator of respiratory capacity. Finally, this was the first study to demonstrate that acute mitochondrial dysfunction in brown fat caused whole-body insulin resistance.

“Circadian metabolism in the light of evolution”
Published in Endocrine Reviews in 2015, this Review explores the role of the body's internal clocks in the hard-wiring of circadian networks that have evolved to achieve energetic balance and adaptability. The article further expounds on potential therapeutic strategies to reset clock metabolic control for the benefit of human health.

Staff of the Gerhart-Hines Group

Group leader: Associate Professor: Zach Gerhart-Hines