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After ingestion, folate from food is hydrolyzed in the gut, where it is converted first to tetrahydrofolate by the enzyme dihydrofolate reductase and then to the active form 5-MTHF, by the enzyme MTHFR

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176 In particular, C18- and C16-long-chain ceramides that are produced by ceramide synthase isoforms (CerS1, CerS5, and CerS6) have higher concentrations in insulin-resistant tissues

Despite this promising anti-diabetic activity of TGR5 mediate by GLP-1 (345), its pharmacological activation in diabetic patients has shown side effects at the level of gallbladder and heart, hampering its clinical use (346)

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