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. 2022 Aug 8;133(5):2915–2930. doi: 10.1111/jam.15740

FIGURE 2.

FIGURE 2

Mechanism of action of GPCRs. SCFAs bind to GPR41 and GPR43 in the distal intestine to produce the intestinal hormones, namely PYY and GLP‐1, which affect satiety and glucose homeostasis. In brown adipocytes, SCFAs directly promote the expression of peroxisome PGC‐1α and UCP1 through a GPR43‐independent pathway, thus increasing fatty acid oxidation. Activation of GPR109A in the adipocyte results in inhibition of adenylate cyclase activity and subsequent reduction in cAMP levels and PKA and HSL/ATGL activity. This results in reduced hydrolysis of TG and subsequent suppression of FFA and glycerol release from the adipocytes. At the same time, adipocytic secretion of adiponectin is increased. The reduction in substrate availability to the liver limits TG and VLDL synthesis and subsequently reduces serum concentration of TG and LDL‐C and increases that of HDL‐C. GPCR, G‐protein‐coupled receptor; PYY, peptide YY; GLP‐1, glucagon‐like peptide‐1; PGC‐1α, peroxisome proliferator‐activated receptor γ coactivator‐1α; UCP1, uncoupling protein 1; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; HSL, hormone sensitive lipase; ATGL, adipose triglyceride lipase; TG, triglyceride; FFA, free fatty acid; VLDL, very low‐density lipoprotein; LDL‐C, low‐density lipoprotein cholesterol; HDL‐C, high‐density lipoprotein cholesterol.