Researchers in the field of health and medicine are racing to make new discoveries in the ongoing battle against obesity and its associated chronic morbidities. In a study published just this month, researchers in Germany and Finland uncovered a connection between brown adipose tissue (BAT), gut hormones, and the brain’s pathways involved in satiation and signaling to stop eating. This regulation pathway is much more complex than scientists recently believed and is still not completely understood.
Brown fat or brown adipose tissue has been known to generate heat in mammals through a process called non-shivering thermogenesis in response to cold exposure. Unlike white adipocytes, which primarily function in storing fat as an energy reserve, brown adipocytes are packed full of mitochondria and express uncoupling protein-1 (UCP-1) which has a unique ability of diminishing the proton gradient across the inner mitochondrial membrane created in the electron transport chain generating heat rather than synthesizing ATP (Rosen & Spiegelman, 2006). This recently published study by Yongguo et al. has found that BAT functions as more than just a heat generator and has effects on metabolism and satiation via gut hormones. The peptide hormone secretin signals the pancreas to secrete bicarbonate into the duodenum of the small intestine during food digestion to neutralize the acidic chyme coming from the stomach and aiding in digestion. Several other hormones are involved in food digestion, but secretin receptors (SCTR) are the most abundant in BAT (Yongguo, et al. 2018). SCTR is a G-protein coupled receptor that induces cAMP-PKA signaling to activate lipolysis in adipocytes. When secretin binds to SCTR and activates lipolysis in brown adipocytes, the free fatty acids released activate UCP1 and thermogenesis (Braun et al. 2018). The researchers in this newest study hypothesized that secretin would induce satiation and alleviate hunger through the BAT activation. They found that the rise in temperature associated with BAT thermogenesis via UCP1 activation was associated with feeding termination in mice. When the BAT associated temperature peaked, the mice stopped eating indicating a correlation between secretin signaling and the thermogenic functions of brown adipocytes resulting in inhibitory control of food intake. This is a unique finding because it identifies a completely different thermogenic mechanism that indicates satiation to the brain; the known pathways already include parasympathetic signaling via vagal afferent nerves in the intestine as well as other key satiating hormones such as ghrelin and amylin that only reach the brain via systemic blood circulation (Yongguo, et al. 2018).
This is an exciting study involving brown adipose tissue and discovering its complexities beyond what we already know about its thermogenic properties. Of course, more research needs to be pursued to further evaluate the pathway and actually how the BAT thermogenic response induces a halt in feeding. Additionally, the study was primarily performed with mice who have a much different BAT dispersion in the body as compared to humans; however, the team has begun studying secretin levels in 17 human subjects following fasting, then after a meal, and are corresponding the levels to metabolically active brown fat (Yongguo, et al. 2018). The researchers in this study attempted to isolate the response of BAT thermogenesis to hunger satiation, however the metabolic and hormonal pathways involved are clearly extremely complicated, so other factors may very well be playing a role in the mice eating patterns observed. Future studies can also concentrate on ways to target this unique brown adipose tissue functionality when treating obesity and metabolic diseases.
Braun, K., Oeckl, J.O., Westermeier, J., et al. (2018). Non-adrenergic control of lipolysis and thermogenesis in adipose tissues. Journal of Experimental Biology. 221. doi:10.1242/jeb.165381.
Cell Press. Gut hormone and brown fat interact to tell the brain it’s time to stop eating. Science Daily. 15 November 2018. <www.sciencedaily.com/releases/2018/11/181115145109.htm>.
Rosen, E.D. & Spiegelman, B.M. (2006). Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 444(7121):847-853. doi:10.1038/nature05483.
Yongguo, L., Schnabl, K., Gabler, S.M., et al. (2018). Secretin-activated brown fat mediates prandial thermogenesis to induce satiation. Cell. DOI: 10.1016/j.cell.2018.10.016.
I just read this paper yesterday and it was really interesting! The researchers emphasize in the discussion the potential for this pathway to be a target for pharmacological or nutritional interventions to treat obesity. In the early 1930s, 2,4-Dinitrophenol was used as a weight loss supplement because it acts as an uncoupling ionophore, similar to UCP-1, and was believed to increase metabolic rate. The drug caused many complications and death in some individuals because the heat produced by the uncoupling channel lead to hyperthermia, with some body temperatures recorded to be as high as 44 degrees Celsius. It seems like the researchers are proposing that the increased temperature as a result of thermogenesis in the brown fat is what signals the brain to trigger satiation. It would be interesting to see if a future drug therapy can actually target this pathway without up-regulating the thermogenic properties of brown fat, which could cause fatal hyperthermia.
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