TY - JOUR
T1 - Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines
T2 - A Randomized Controlled Trial
AU - Telgenkamp, Ine
AU - Kusters, Yvo H. A. M.
AU - Schalkwijk, Casper G.
AU - Houben, Alfons J. H. M.
AU - Kooi, M. Eline
AU - Lindeboom, Lucas
AU - Bons, Judith A. P.
AU - Schaper, Nicolaas C.
AU - Joris, Peter J.
AU - Plat, Jogchum
AU - Mensink, Ronald P.
AU - Stehouwer, Coen D. A.
AU - Brouwers, Martijn C. G. J.
N1 - Funding Information:
Financial Support: This work was supported by European Foundation for the Study of Diabetes (EFSD)/Sanofi and by Grant CH001 from Top Institute of Food and Nutrition, a public/private partnership on precompetitive research in food and nutrition. The public partners are responsible for the study design, data collection and analysis, decision to publish, and preparation of the manuscript.
Publisher Copyright:
© 2019 Endocrine Society.
PY - 2019/7
Y1 - 2019/7
N2 - Context: Hepatokines have emerged as potential mediators of obesity-associated comorbidities, such as type 2 diabetes, cardiovascular disease, fractures, and central hypogonadism.Objective: To assess whether weight loss-induced changes in hepatokines are mediated by intrahepatic triglyceride (IHTG) content.Design: Cross-sectional study and randomized controlled trial.Setting: General community.Participants: Metabolically healthy, lean men (waistIntervention: Men with abdominal obesity were randomized to 8-week dietary weight loss or no weight loss.Main Outcome Measures: IHTG and serum hepatokines, that is, serum IGF1, IGF binding protein 1 (IGFBP1), SHBG, fibroblast growth factor 21 (FGF21), fetuin A, and plasma fetuin B.Results: All hepatokines, except for fetuin B, were significantly different between lean men and men with obesity. After the weight-loss intervention (-10.3 kg; 95% CI, -11.4 to-9.2), serum IGF1, IGFBP1, SHBG, and fetuin A approached the values observed in lean men. Cross-sectional associations were observed between IHTG and IGF1 (beta = -0.51; 95% CI, -0.82 to -0.20), IGFBP1 (beta = -4.2; 95% CI, -7.7 to -0.7), and FGF21 (beta = 2.1; 95% CI, 1.3 to 2.9) in lean men and men with abdominal obesity combined. Weight loss resulted in a reduction of IHTG (treatment effect, -2.2%; 95% CI, -3.4% to -1.2%) that was associated with a change in IGF1 (beta = -0.9; 95% CI, -1.3 to -0.4), IGFBP1 (beta = -0.17; 95% CI, -0.31 to -0.03), and SHBG levels (beta = -0.18; 95% CI, -0.29 to -0.07). Mediation analyses showed that only the weight loss-induced change in serum IGF1 was mediated by IHTG (mediated effect, 32.7%; 95% CI, 4.6% to 79.2%).Conclusions: Dietary weight loss has differential effects on hepatokines. This study shows that the change in serum IGF1 levels after dietary weight loss is mediated by the change in IHTG content.
AB - Context: Hepatokines have emerged as potential mediators of obesity-associated comorbidities, such as type 2 diabetes, cardiovascular disease, fractures, and central hypogonadism.Objective: To assess whether weight loss-induced changes in hepatokines are mediated by intrahepatic triglyceride (IHTG) content.Design: Cross-sectional study and randomized controlled trial.Setting: General community.Participants: Metabolically healthy, lean men (waistIntervention: Men with abdominal obesity were randomized to 8-week dietary weight loss or no weight loss.Main Outcome Measures: IHTG and serum hepatokines, that is, serum IGF1, IGF binding protein 1 (IGFBP1), SHBG, fibroblast growth factor 21 (FGF21), fetuin A, and plasma fetuin B.Results: All hepatokines, except for fetuin B, were significantly different between lean men and men with obesity. After the weight-loss intervention (-10.3 kg; 95% CI, -11.4 to-9.2), serum IGF1, IGFBP1, SHBG, and fetuin A approached the values observed in lean men. Cross-sectional associations were observed between IHTG and IGF1 (beta = -0.51; 95% CI, -0.82 to -0.20), IGFBP1 (beta = -4.2; 95% CI, -7.7 to -0.7), and FGF21 (beta = 2.1; 95% CI, 1.3 to 2.9) in lean men and men with abdominal obesity combined. Weight loss resulted in a reduction of IHTG (treatment effect, -2.2%; 95% CI, -3.4% to -1.2%) that was associated with a change in IGF1 (beta = -0.9; 95% CI, -1.3 to -0.4), IGFBP1 (beta = -0.17; 95% CI, -0.31 to -0.03), and SHBG levels (beta = -0.18; 95% CI, -0.29 to -0.07). Mediation analyses showed that only the weight loss-induced change in serum IGF1 was mediated by IHTG (mediated effect, 32.7%; 95% CI, 4.6% to 79.2%).Conclusions: Dietary weight loss has differential effects on hepatokines. This study shows that the change in serum IGF1 levels after dietary weight loss is mediated by the change in IHTG content.
KW - LIFE-STYLE INTERVENTION
KW - FETUIN-A
KW - GROWTH-HORMONE
KW - CALORIE RESTRICTION
KW - CIRCULATING LEVELS
KW - HEPATIC STEATOSIS
KW - RISK
KW - OBESITY
KW - FGF21
KW - OVERWEIGHT
U2 - 10.1210/jc.2018-02378
DO - 10.1210/jc.2018-02378
M3 - Article
C2 - 30753672
SN - 0021-972X
VL - 104
SP - 2719
EP - 2727
JO - Journal of Clinical Endocrinology & Metabolism
JF - Journal of Clinical Endocrinology & Metabolism
IS - 7
ER -