Zach Gerhart-Hines, PhD

Associate Professor
NNF CBMR, University of Copenhagen

What is your presentation about?

My presentation describes the discovery and characterization of SLC25A34, a previously uncharacterized mitochondrial metabolite transporter that integrates circadian clock signals, dietary cues, and environmental temperature to coordinate thermogenic lipid metabolism in adipocytes. During sleep, the circadian repressors REV-ERBα and REV-ERBβ suppress SLC25A34 expression; upon waking, cold exposure, or consumption of lipid-rich diets, this repression is lifted and PPARα/γ drive transporter expression. SLC25A34 imports oxaloacetate into mitochondria to sustain TCA cycle flux and cytosolic acetyl-CoA production, thereby fueling both de novo lipogenesis and transcriptional upregulation of mitochondrial oxidative capacity. We further show that in human subcutaneous white adipose tissue, SLC25A34 expression correlates favorably with markers of cardiometabolic health, including lower BMI, triglycerides, and HOMA-IR.

How do you hope your presentation will impact diabetes research or care?

Adipose tissue metabolism plays a central role in energy balance and is associated with improved glucose homeostasis, insulin sensitivity, and cardiometabolic health. Thus, the underlying molecular machinery controlling adipose tissue functions represent compelling therapeutic targets for obesity and type 2 diabetes. By identifying SLC25A34 as a key node integrating the circadian clock, diet, and temperature in adipocytes, our work opens a new avenue for developing strategies that harness adipose lipid cycling to combat the caloric excess and metabolic dysregulation driving diabetes. The strong associations between SLC25A34 expression and clinically relevant metabolic parameters in human adipose tissue suggest this transporter may have direct translational relevance for improving glucose and lipid homeostasis in patients.

How did you become involved with this area of diabetes research or care?

My laboratory has long been interested in how the circadian clock controls energy metabolism in adipose tissue, with a particular focus on how thermogenic brown and beige adipocytes can be leveraged to counteract the metabolic dysfunction underlying obesity and type 2 diabetes. This project emerged from a systematic multi-omic approach we undertook to identify the molecular factors that mediate the daily rhythms and acute temperature responses of adipose thermogenesis. Uncovering SLC25A34 as a metabolic integrator at the intersection of circadian biology, nutrition, and temperature physiology has deepened our commitment to understanding how these fundamental biological programs can be therapeutically exploited for metabolic disease.