The gut hormone secretin triggers a gut–brown fat–brain axis in the control of food intake

Abstract

Brown fat research concentrates on the energy expenditure function of this heating organ, whereas previous evidence for a role of brown fat in regulating energy intake has been mostly neglected. Ingestion of a single mixed meal activates human brown fat thermogenesis to the same degree as cold. In mice, activation of brown fat thermogenesis with a 3-adrenergic receptor agonist inhibits food intake. Pharmacological-blockade, however, inhibits neither mealassociated thermogenesis nor food intake. We recently identified the gut hormone secretin as a non-adrenergic activator of brown fat. In vivo, secretin treatment acutely increases energy expenditure and inhibits food intake in wild-type, but not in uncoupling protein 1 (UCP1)knockout (KO) mice, which lack thermogenic brown fat function. Concurrently, secretin alters gene expression of melanocortinergic peptides of hypothalamic neurons in wild-type mice, but not UCP1-KO. Blocking endogenous secretin with a neutralizing antibody attenuates brown fat thermogenesis during refeeding, increases food intake of mice, and alters ad libitum feeding behaviour. Taken together, these findings demonstrate that secretin triggers an endocrine gutbrown adipose tissue-brain axis in the control of satiation. We hypothesize that meal-associated activation of brown adipose tissue thermogenesis induced by secretin results in a rise in brain temperature and increased melanocortinergic signalling. Taken together, brown fat is not a mere heating organ dissipating excess calories but also involved in gut-brain communication in the control of food intake.

Crosstalk between adipose tissue and the microbiota-gut-brain axis in metabolic diseases

“…Following clinical randomized controlled trials demonstrate that, in human, secretin also ignite metabolic regulation feature of BAT, which not only optimizes glucose uptake efficiency in BAT, but suppresses appetite, as well as delaying resumption to eat after a meal [131]. Unlike the mechanism by which GLP-1 and CCK induce thermogenesis in BAT, the non-selective beta blocker propranolol did not affect the thermogenesis in BAT and central satiation variation induced by secretin, ruling out the regulatory role of the gut-brain-BAT axis in terms of BAT thermogenesis induced by secretin [59,132]. In this context, BAT could act as a medium for intestinal hormone regulation of central metabolic signals.…”

The colorful versatility of adipocytes: white‐to‐brown transdifferentiation and its therapeutic potential in humans

“…Although food intake stimulates human BAT activity to a similar degree as cold exposure, it is unlikely that chronic secretin is sufficiently capable of achieving significant weight loss [197,199]. Combination strategies of drugs acting on increasing energy expenditure with drugs acting on reducing food intake may act more potently to achieve synergistic weight loss [200].…”

Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum

“…The hypothesis of a “fat–brain axis” [ 1 , 2 ] is that adipocyte-specific secretory hormones, proteins and peptides are released by white adipocytes (“ adipokines ”) or brown adipocytes (“ batokines ” ) into the circulation, cross over the blood–brain barrier (BBB), appear in cerebrospinal fluid (CSF) and finally regulate central nervous system functions such as appetite, satiety, sympathetic neural outflow, temperature, energy expenditure, pituitary and hypothalamic function, stress reaction, energy appeal reaction and others [ 3 , 4 , 5 ]. The very first identified and most prominent mediator of the fat–brain axis is represented by the satiety hormone leptin [ 2 ].…”