Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial

Ine Telgenkamp; Yvo H A M Kusters; Casper G Schalkwijk; Alfons J H M Houben; M Eline Kooi; Lucas Lindeboom; Judith A P Bons; Nicolaas C Schaper; Peter J Joris; Jogchum Plat; Ronald P Mensink; Coen D A Stehouwer; Martijn C G J Brouwers

doi:10.1210/jc.2018-02378

Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial

Ine Telgenkamp, Yvo H A M Kusters, Casper G Schalkwijk, Alfons J H M Houben, M Eline Kooi, Lucas Lindeboom, Judith A P Bons, Nicolaas C Schaper, Peter J Joris, Jogchum Plat, Ronald P Mensink, Coen D A Stehouwer, Martijn C G J Brouwers

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 (waist <94 cm; n = 25) and men with abdominal obesity (waist 102 to 110 cm; n = 52).

INTERVENTION: 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 (β = -0.51; 95% CI, -0.82 to -0.20), IGFBP1 (β = -4.2; 95% CI, -7.7 to -0.7), and FGF21 (β = 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 (β = -0.9; 95% CI, -1.3 to -0.4), IGFBP1 (β = -0.17; 95% CI, -0.31 to -0.03), and SHBG levels (β = -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.

Original language	English
Pages (from-to)	2719-2727
Number of pages	9
Journal	The Journal of Clinical Endocrinology & Metabolism
Volume	104
Issue number	7
DOIs	https://doi.org/10.1210/jc.2018-02378
Publication status	Published - 11 Feb 2019
Externally published	Yes

Keywords

adult
case-control studies
cross-sectional studies
diet, reducing
fetuin-B/metabolism
fibroblast growth factors/metabolism
humans
insulin-like growth factor binding protein 1/metabolism
insulin-like growth factor I/metabolism
liver/metabolism
male
middle aged
obesity, abdominal/diet therapy
sex hormone-binding globulin/metabolism
triglycerides/metabolism
weight loss
alpha-2-HS-glycoprotein/metabolism

Access to Document

10.1210/jc.2018-02378Licence: Unspecified

Cite this

Telgenkamp, I., Kusters, Y. H. A. M., Schalkwijk, C. G., Houben, A. J. H. M., Kooi, M. E., Lindeboom, L., Bons, J. A. P., Schaper, N. C., Joris, P. J., Plat, J., Mensink, R. P., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2019). Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial. The Journal of Clinical Endocrinology & Metabolism, 104(7), 2719-2727. https://doi.org/10.1210/jc.2018-02378

@article{e388c9b18b254124a19e10a7b3ace027,

title = "Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial",

abstract = "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 (waist <94 cm; n = 25) and men with abdominal obesity (waist 102 to 110 cm; n = 52).INTERVENTION: 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 (β = -0.51; 95\% CI, -0.82 to -0.20), IGFBP1 (β = -4.2; 95\% CI, -7.7 to -0.7), and FGF21 (β = 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 (β = -0.9; 95\% CI, -1.3 to -0.4), IGFBP1 (β = -0.17; 95\% CI, -0.31 to -0.03), and SHBG levels (β = -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.",

keywords = "adult, case-control studies, cross-sectional studies, diet, reducing, fetuin-B/metabolism, fibroblast growth factors/metabolism, humans, insulin-like growth factor binding protein 1/metabolism, insulin-like growth factor I/metabolism, liver/metabolism, male, middle aged, obesity, abdominal/diet therapy, sex hormone-binding globulin/metabolism, triglycerides/metabolism, weight loss, alpha-2-HS-glycoprotein/metabolism, volwassene, case-cohort onderzoek, cross-sectionele studies, dieet, verminderen, fetuin-B/metabolisme, fibroblastgroeifactoren/metabolisme, mensen, insuline-achtige groeifactor-bindend eiwit 1/metabolisme, insuline-achtige groeifactor I/metabolisme, lever/metabolisme, mannelijk, middelbare leeftijd, zwaarlijvigheid, buik-/dieettherapie, geslachtshormoonbindend globuline/metabolisme, triglyceriden/metabolisme, gewichtsverlies, alfa-2-HS-glycoprote{\"i}ne/metabolisme",

author = "Ine Telgenkamp and Kusters, \{Yvo H A M\} and Schalkwijk, \{Casper G\} and Houben, \{Alfons J H M\} and Kooi, \{M Eline\} and Lucas Lindeboom and Bons, \{Judith A P\} and Schaper, \{Nicolaas C\} and Joris, \{Peter J\} and Jogchum Plat and Mensink, \{Ronald P\} and Stehouwer, \{Coen D A\} and Brouwers, \{Martijn C G J\}",

note = "Copyright {\textcopyright} 2019 Endocrine Society.",

year = "2019",

month = feb,

day = "11",

doi = "10.1210/jc.2018-02378",

language = "English",

volume = "104",

pages = "2719--2727",

journal = "The Journal of Clinical Endocrinology \& Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

number = "7",

}

Telgenkamp, I, Kusters, YHAM, Schalkwijk, CG, Houben, AJHM, Kooi, ME, Lindeboom, L, Bons, JAP, Schaper, NC, Joris, PJ, Plat, J, Mensink, RP, Stehouwer, CDA & Brouwers, MCGJ 2019, 'Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial', The Journal of Clinical Endocrinology & Metabolism, vol. 104, no. 7, pp. 2719-2727. https://doi.org/10.1210/jc.2018-02378

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

PY - 2019/2/11

Y1 - 2019/2/11

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 (waist <94 cm; n = 25) and men with abdominal obesity (waist 102 to 110 cm; n = 52).INTERVENTION: 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 (β = -0.51; 95% CI, -0.82 to -0.20), IGFBP1 (β = -4.2; 95% CI, -7.7 to -0.7), and FGF21 (β = 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 (β = -0.9; 95% CI, -1.3 to -0.4), IGFBP1 (β = -0.17; 95% CI, -0.31 to -0.03), and SHBG levels (β = -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 (waist <94 cm; n = 25) and men with abdominal obesity (waist 102 to 110 cm; n = 52).INTERVENTION: 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 (β = -0.51; 95% CI, -0.82 to -0.20), IGFBP1 (β = -4.2; 95% CI, -7.7 to -0.7), and FGF21 (β = 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 (β = -0.9; 95% CI, -1.3 to -0.4), IGFBP1 (β = -0.17; 95% CI, -0.31 to -0.03), and SHBG levels (β = -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 - adult

KW - case-control studies

KW - cross-sectional studies

KW - diet, reducing

KW - fetuin-B/metabolism

KW - fibroblast growth factors/metabolism

KW - humans

KW - insulin-like growth factor binding protein 1/metabolism

KW - insulin-like growth factor I/metabolism

KW - liver/metabolism

KW - male

KW - middle aged

KW - obesity, abdominal/diet therapy

KW - sex hormone-binding globulin/metabolism

KW - triglycerides/metabolism

KW - weight loss

KW - alpha-2-HS-glycoprotein/metabolism

KW - volwassene

KW - case-cohort onderzoek

KW - cross-sectionele studies

KW - dieet, verminderen

KW - fetuin-B/metabolisme

KW - fibroblastgroeifactoren/metabolisme

KW - mensen

KW - insuline-achtige groeifactor-bindend eiwit 1/metabolisme

KW - insuline-achtige groeifactor I/metabolisme

KW - lever/metabolisme

KW - mannelijk

KW - middelbare leeftijd

KW - zwaarlijvigheid, buik-/dieettherapie

KW - geslachtshormoonbindend globuline/metabolisme

KW - triglyceriden/metabolisme

KW - gewichtsverlies

KW - alfa-2-HS-glycoproteïne/metabolisme

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 - The Journal of Clinical Endocrinology & Metabolism

JF - The Journal of Clinical Endocrinology & Metabolism

IS - 7

ER -

Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial

Abstract

Keywords

Access to Document

Fingerprint

Cite this