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Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity
Author(s) -
Straniero S.,
Rosqvist F.,
Edholm D.,
Ahlström H.,
Kullberg J.,
Sundbom M.,
Risérus U.,
Rudling M.
Publication year - 2017
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12599
Subject(s) - medicine , endocrinology , fgf19 , cholesterol , calorie , bile acid , excretion , fgf21 , fibroblast growth factor , receptor
Background Bile acid ( BA ) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 ( FGF 19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BA s and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BA s and cholesterol, thereby creating a shortage of both BA s and cholesterol in the liver. Methods Ten morbidly obese women ( BMI 42 ± 2.6 kg m −2 ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low‐calorie diet (800–1100 kcal day −1 ). Serum was collected and liver size and fat content determined. Synthesis of BA s and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BA s, proprotein convertase subtilisin/kexin type 9 ( PCSK 9), insulin, glucose and FGF 19 were monitored. Fifty‐four nonobese women ( BMI <25 kg m −2 ) served as controls. Results At baseline, synthesis of both BA s and cholesterol and serum levels of BA s and PCSK 9 were elevated in the obese group compared to controls. Already after 3 days on a low‐calorie diet, BA and cholesterol synthesis and serum BA and PCSK 9 levels normalized, whereas LDL cholesterol increased. FGF 19 and triglyceride levels were unchanged, and liver volume was reduced by 10%. Conclusions The results suggest that hepatic BA s and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK 9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BA s and cholesterol contributing to their hepatic deficiencies.