When pigs fly, UCP1 makes heat

Abstract

Brown and beige adipose tissue may represent important therapeutic targets for the treatment of diabetes and obesity as these organs dissipate nutrient energy as heat through the thermogenic uncoupling protein 1 (UCP1). While mice are commonly used to mimic the potential effects of brown/beige adipose tissue that may act in human metabolism, new animal models are edging into the market for translational medicine. Pigs reflect human metabolism better than mice in multiple parameters such as obesity-induced hyperglycemia, cholesterol profiles and energy metabolism. Recently, it was reported that energy expenditure and body temperature in pigs is induced by the hormone leptin, and that leptin's action is mediated by UCP1 in adipose tissue. Given the tremendous importance of identifying molecular mechanisms for targeting therapeutics, we critically examine the evidence supporting the presence of UCP1 in pigs and conclude that methodological shortcomings prevent an unequivocal claim for the presence of UCP1 in pigs. Despite this, we believe that leptin's effects on energy expenditure in pigs are potentially more transformative to human medicine in the absence of UCP1, as adult and obese humans possess only minor amounts of UCP1. In general, we propose that the biology of new animal models requires attention to comparative studies with humans given the increasing amount of genomic information for various animal species.

Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research

“…BAT has been detected in a small subset of human adults [145]; however, this tissue exhibited molecular characteristics of beige rather than classical brown fat cells [146]. Pigs do not have a functional UCP1 gene [75]. Therefore, pigs resemble human adults better than rodent models, enabling the study of UCP1-independent remodeling processes of WAT.…”

Nature's fat-burning machine: brown adipose tissue in a hibernating mammal

“…Heat production is made possible by the numerous BAT mitochondria, which uniquely contain UCP1. UCP1 is a BAT-specific transport protein of the inner mitochondrial membrane (as reviewed by Nicholls and Locke, 1984;Cannon and Nedergaard, 2004), and is present in most placental mammals (Jastroch and Andersson, 2015;Gaudry et al, 2017). UCP1 is activated by long-chain fatty acids (as reviewed by Klingenberg and Huang, 1999;Fedorenko et al, 2012), and activation of UCP1 (A) Passive whole-body cooling that occurs during 'entry into torpor' is almost as abrupt as the warming during 'arousal'.…”

Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology

“…Two recent studies also indicate that ovine adipose tissue undergoes pronounced changes in cell composition and gene expressions between mid-gestation and 1 month of age (Pope et al, 2013;Basse et al, 2015), leading to a gradual disappearance of brown adipocytes. The pig neonate with its lack of BAT represents an exception among mammals (Trayhurn et al, 1989;Jastroch and Andersson, 2015).…”