Formation of thermogenic adipocytes: What we have learned from pigs

Thermogenic adipocytes, including brown and beige adipocytes, are capable of dissipating energy via heat production in response to external stimuli, such as cold exposure and exercise. This distinct feature makes them promising targets for therapy of obesity and related metabolic disease. In most mammals, the thermogenic function relies on uncoupling protein 1 (UCP1), which creates a proton leak across the inner mitochondrial membrane, diverting protons away from ATP synthesis and resulting in heat dissipation. However, that is not the case in pigs. Accumulating evidence suggested that in pigs neither functional UCP1 nor brown adipocytes were identified, which might be the leading cause for cold stress-caused neonatal mortality and greater adiposity. In our previous study, beige adipocyte formation was found in cold-tolerant pig breeds, together with the finding that UCP1 knock-in improved thermoregulatory ability and decreased fat deposition in pigs, suggesting the potential application of beige induction in pigs for both agricultural purpose and biomedical implication. In this context, we review the anatomical features, developmental origins, plasticity, transcriptional regulation, and the metabolic benefits of thermogenic adipocytes. Particularly, we describe the contribution of beige adipocytes and reconstitution of UCP1 to improve cold sensitivity and decrease fat deposition in pigs. Furthermore, future undertaking regarding beige adipocyte formation in pigs and its potential application is also discussed.