Dietary Medium-Chain Triglyceride Decanoate Affects Glucose Homeostasis Through GPR84-Mediated GLP-1 Secretion in Mice

Abstract

BackgroundDietary triglycerides are an important energy source; however, their excess intake causes metabolic diseases such as obesity and type 2 diabetes. Medium-chain triglycerides (MCTs) as triglyceride forms of medium-chain fatty acids (MCFAs) are applied to meet the energy demands of athletes, the elderly, and people with stunted growth, because MCFAs are efficiently converted into energy for immediate utilization by the organs and do not accumulate as fat. Although the intake of each MCT type (octanoate; C8:0, decanoate; C10:0, and dodecanoate; C12:0) exhibits beneficial metabolic effects, individual functional differences remain unclear.MethodsMCTs or MCFAs were administrated to male GPR84-deficient mice with a C57BL/6J background and mouse enteroendocrine cell line STC-1, and the effects on glucose homeostasis and gut hormone GLP-1 secretion were evaluated.ResultsC10:0 intake improves glucose metabolism through the MCFA receptor GPR84-mediated GLP-1 secretion. Each MCT intake showed resistance to obesity and improved metabolic parameters compared with lard intake. Moreover, oral administration of MCTs enhanced glucose tolerance, especially C10:0 administration, which sufficiently increased plasma GLP-1 levels. Additionally, C10:0 stimulation promoted GLP-1 secretion via GPR84 in STC-1, enhanced glucose tolerance through GPR84-mediated GLP-1 secretion, and showed resistance to high-fat diet (HFD)-induced obesity in mice.ConclusionsDietary MCT (C10:0) intake efficiently may protect against obesity and improve insulin resistance via GLP-1 secretion.

Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84

“…Metabolic disorders, such as obesity, insulin resistance, glucose intolerance, and type 2 diabetes, are significant risk factors of NASH ( 4 , 5 ). We recently reported that MCFA-stimulated GPR84 activation maintains glucose homeostasis by insulin regulation via glucagon-like peptide-1 (GLP-1) secretion ( 25 ). GLP-1 also suppresses the proinflammatory and profibrotic phenotypes of macrophages, thereby suppressing NASH development ( 31 , 32 ).…”

“…GPR84 is coupled with the pertussis toxin-sensitive Gi/o protein and is predominantly expressed in the bone marrow, lungs, and peripheral leucocytes (13,14,21). Although some studies on GPR84-deficient mice have demonstrated that GPR84 plays an important role in immune and metabolic responses and may mediate the crosstalk between immune cells and adipocytes (22)(23)(24)(25), comprehensive and integrated data bridging the gap between endogenous MCFAs and GPR84 are lacking, and the molecular mechanisms underlying these processes remain unclear.…”

Timing of Medium-Chain Triglyceride Consumption Modulates Effects in Mice with Obesity Induced by a High-Fat High-Sucrose Diet

“…Murata et al [ 33 , 34 ] found that dietary MCT prevents diet-induced obesity by inhibiting LCT-induced GIP secretion in mice. Ingesting MCTs containing only capric acid increases plasma GLP-1 levels that suppress obesity and insulin resistance induced by HFD in mice [ 35 ]. Daily feeding and fasting cycles affect fluctuations in blood GLP-1 and GIP [ 36 , 37 ].…”

Distinct impacts of fat and fructose on the liver, muscle, and adipose tissue metabolome: An integrated view

“…Experiments were performed using male C57Bl6/J mice kept on a 12-h light/dark cycle with ad libitum access to food and water. Animals were randomly divided in three groups (n=7/ group) and fed different diets from 6…”

“…However, fats and specifically triglycerides are differently metabolized depending on the fatty acid chain length. While medium-chain triglycerides are absorbed into the portal circulation and transported to the liver, long-chain fatty acids are transported through the lymphatic system via chylomicrons ( 6 ).…”