Chenodeoxycholic acid therapy for hypertriglyceridaemia in men.

Abstract

I Ten consecutive patients with hypertriglyceridaemia who adhered to a low carbohydrate diet without complete control of serum triglycerides were started on chenodeoxycholic acid 750 mg daily and followed monthly for 6 months. Nine of these patients were then followed for a further month on placebo capsules and thereafter monthly for a further 6 months on clofibrate 2 g daily. 2 The mean serum triglyceride level fell by 36% after dietary treatment alone (P <0.05) and by 47% from initial values on diet plus chenodeoxycholic acid (P < 0.01). In the nine patients who proceeded to clofibrate therapy there was a rise in triglyceride levels on placebo capsules to the level achieved by diet alone, and a further fall on diet plus clofibrate of 47% of initial values (P < 0.05). 3 Chenodeoxycholic acid therapy is effective in the management of hypertriglyceridaemia not completely cured by dietary measures, and may be as efficacious as clofibrate.

Coordinated control of bile acids and lipogenesis through FXR-dependent regulation of fatty acid synthase

“…The first evidence that bile acids might be involved in fatty acid metabolism derived from the incidental observation .20 years ago that administration of bile acids decreased serum triglycerides in patients with gallstone disease (19)(20)(21)). An FXR-dependent mechanism for this effect was proposed by Watanabe et al (22), who observed that SREBP-1c levels decreased z50% but SHP levels increased by 300% after 1 day of treatment of wildtype or prediabetic (KK-A y ) mice with 0.5% cholic acid.…”

“…The triglyceride-lowering effect of bile acids was first described .20 years ago when clinicians ob-served that bile acid therapy for the treatment of gallstone disease had the added effect of decreasing serum triglycerides (19)(20)(21). More recently, FXR induction of its target gene SHP was shown to correlate with decreased expression of the master lipogenic regulator sterolregulatory element binding protein (SREBP)-1c (as well as many of its gene targets), thus providing at least a partial mechanistic explanation for the triglyceride-lowering effect of bile acids (22).…”

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

“…In vitro, FXR activation in a human hepatocyte cell line decreases MTP expression and the secretion of VLDL ( 54 ). Consequently, the administration of CDCA to patients with hypertriglyceridemia reduces plasma TG ( 55,56 ).…”

“…Four studies in small patient cohorts (n = 8-15) fi nd a reduction in plasma TG ( 55,56,105,106 ) but no change in total plasma cholesterol ( 55,56,106 ), and one reports decreased HDL-C levels ( 105 ). The only study conducted in a large number of patients (n = 916) observes an increase of LDL-C upon CDCA administration ( 36 ).…”

Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c

“…In humans, bile acid-binding resins induce the production of VLDL TGs (12)(13)(14), whereas treatment of cholesterol gallstones with the bile acid chenodeoxycholic acid (CDCA) has been shown to reduce hypertriglyceridemia (12,15,16). The mechanism underlying this reciprocal relationship between bile acid biosynthesis and TG production has remained elusive, but two possible explanations have been postulated.…”