BMP8 and activated brown adipose tissue in human newborns

Abstract

The classical dogma states that brown adipose tissue (BAT) plays a major role in the regulation of temperature in neonates. However, although BAT has been studied in infants for more than a century, the knowledge about its physiological features at this stage of life is rather limited. This has been mainly due to the lack of appropriate investigation methods, ethically suitable for neonates. Here, we have applied non-invasive infrared thermography (IRT) to investigate neonatal BAT activity. Our data show that BAT temperature correlates with body temperature and that mild cold stimulus promotes BAT activation in newborns. Notably, a single short-term cold stimulus during the first day of life improves the body temperature adaption to a subsequent cold event. Finally, we identify that bone morphogenic protein 8B (BMP8B) is associated with the BAT thermogenic response in neonates. Overall, our data uncover key features of the setup of BAT thermogenesis in newborns.

Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase

“…• T3 (0.5 mg/L T3 in 0.01% BSA) TREATMENT START SACRIFICE Core body temperature was measured at the end of the treatment using a rectal probe connected to digital thermometer (BAT-12 Microprobe Thermometer; Physitemp; Clifton, NJ, USA). Skin temperature surrounding BAT, as well as the temperature at the base of the tail, were recorded at the end of the treatment with an infrared camera (B335: Compact Infrared Thermal-Imaging Camera; FLIR; West Malling, Kent, UK) and analyzed with a specific software package (FLIR Tools Software, FLIR; West Malling, Kent, UK), as previously shown [16,[35][36][37][38][39][40][41][42][43][44][45]. For each image, the average temperatures were calculated as the average of 2 pictures/animal.…”

Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome

“…BMP8B, a member of the TGFβ-BMP superfamily, has recently emerged as a key secreted factor regulating energy balance through endocrine and paracrine actions [ [21] , [22] , [23] , [24] , [25] ]. Several studies have reported that central BMP8B promotes BAT thermogenesis and WAT browning through modulation of hypothalamic AMPK [ 21 , 22 ].…”

“…Further work involving BBS1 overexpression in specific neuronal populations in the context of obesity, as well as the SF1 BBS1 KO mice that we have recently generated and reported [ 19 ], will shed new light about the mechanistic link between BMP8B and the BBSome. Considering the recently discovered involvement of BMP8B in the regulation of metabolism in humans [ 24 , 25 ], this evidence suggests that resistance to BMP8B could be a pathological mechanism of common human obesity.…”

“…Current data point to BMP8B as a major molecule in whole body metabolism by modulating i) brown adipose tissue (BAT) thermogenesis and the browning of white adipose tissue (WAT), through its action on AMP-activated protein kinase (AMPK) in the ventromedial nucleus of the hypothalamus (VMH) [ [21] , [22] , [23] ]; ii) the remodeling of the neuro-vascular network in adipose tissue acting through paracrine actions [ 23 ]; and iii) hepatic lipid metabolism and inflammation [ 24 ]. Notably, the relevance of BMP8B has been demonstrated in humans, and current data have also linked BMP8B to the progression of non-alcoholic steatohepatitis [ 24 ], as well as to the thermogenic response in babies [ 25 ]. Considering this evidence, the aim of this study was to investigate i) whether BMP8B role in metabolism is affected by obesity and ii) the molecular mechanisms underlying possible resistance to BMP8B actions on energy homeostasis.…”

Core Temperature Measurement—Principles of Correct Measurement, Problems, and Complications

“…In newborns, the blood flow is additionally modified, causing peripheral cyanosis. Finally, newborns lack the shivering mechanism and have to depend on non-shivering thermogenesis [12].…”