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Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes.

Berti L, Irmler M, Zdichavsky M, Meile T, Böhm A, Stefan N, Fritsche A, Beckers J, Königsrainer A, Häring HU, de Angelis MH, Staiger H - Mol Metab (2015)

Bottom Line: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type-2 diabetes, and the metabolic syndrome.FGF21 treatment of human preadipocytes for the entire differentiation period was modestly lipogenic (+15%; p < 0.05), reduced the expression of key adipogenic transcription factors (PPARG and CEBPA, -15% and -40%, respectively; p < 0.01 both), reduced adiponectin expression (-20%; p < 0.05), markedly reduced adiponectin release (-60%; p < 0.01), and substantially increased leptin (+60%; p < 0.01) and interleukin-6 (+50%; p < 0.001) release.The hepatokine FGF21 exerts weak lipogenic and anti-adipogenic actions and marked adiponectin-suppressive and leptin and interleukin-6 release-promoting effects in human differentiating preadipocytes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Experimental Genetics, Helmholtz Centre Munich GmbH, German Research Centre for Environmental Health, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany ; German Centre for Diabetes Research (DZD), Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.

ABSTRACT

Objective: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type-2 diabetes, and the metabolic syndrome. We asked whether FGF21 levels differ between subjects with metabolically healthy vs. unhealthy obesity (MHO vs. MUHO), opening the possibility that FGF21 is a cross-talker between liver and adipose tissue in MUHO. Furthermore, we studied the effects of chronic FGF21 treatment on adipocyte differentiation, lipid storage, and adipokine secretion.

Methods: In 20 morbidly obese donors of abdominal subcutaneous fat biopsies discordant for their whole-body insulin sensitivity (hereby classified as MHO or MUHO subjects), serum FGF21 was quantified. The impact of chronic FGF21 treatment on differentiation, lipid accumulation, and adipokine release was assessed in isolated preadipocytes differentiated in vitro.

Results: Serum FGF21 concentrations were more than two-fold higher in MUHO as compared to MHO subjects (457 ± 378 vs. 211 ± 123 pg/mL; p < 0.05). FGF21 treatment of human preadipocytes for the entire differentiation period was modestly lipogenic (+15%; p < 0.05), reduced the expression of key adipogenic transcription factors (PPARG and CEBPA, -15% and -40%, respectively; p < 0.01 both), reduced adiponectin expression (-20%; p < 0.05), markedly reduced adiponectin release (-60%; p < 0.01), and substantially increased leptin (+60%; p < 0.01) and interleukin-6 (+50%; p < 0.001) release.

Conclusions: The hepatokine FGF21 exerts weak lipogenic and anti-adipogenic actions and marked adiponectin-suppressive and leptin and interleukin-6 release-promoting effects in human differentiating preadipocytes. Together with the higher serum concentrations in MUHO subjects, our findings reveal FGF21 as a circulating factor promoting the development of metabolically unhealthy adipocytes.

No MeSH data available.


Related in: MedlinePlus

Serum FGF21 concentrations in MHO and MUHO subjects Data adjusted for gender, age, and BMI are shown as log-transformed individual data and means ± SD (N = 10 per group). Adjustment was performed by multiple linear regression modeling. MHO – metabolically healthy obesity; MUHO – metabolically unhealthy obesity.
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fig1: Serum FGF21 concentrations in MHO and MUHO subjects Data adjusted for gender, age, and BMI are shown as log-transformed individual data and means ± SD (N = 10 per group). Adjustment was performed by multiple linear regression modeling. MHO – metabolically healthy obesity; MUHO – metabolically unhealthy obesity.

Mentions: After adjustment for the putative confounders gender, age, and BMI by multiple linear regression modeling, serum FGF21 concentrations were more than twice as high in MUHO subjects as compared to MHO subjects (unadjusted 457 ± 378 vs. 211 ± 123 pg/mL, means ± SD; adjusted data presented in Figure 1; p = 0.023).


Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes.

Berti L, Irmler M, Zdichavsky M, Meile T, Böhm A, Stefan N, Fritsche A, Beckers J, Königsrainer A, Häring HU, de Angelis MH, Staiger H - Mol Metab (2015)

Serum FGF21 concentrations in MHO and MUHO subjects Data adjusted for gender, age, and BMI are shown as log-transformed individual data and means ± SD (N = 10 per group). Adjustment was performed by multiple linear regression modeling. MHO – metabolically healthy obesity; MUHO – metabolically unhealthy obesity.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4481465&req=5

fig1: Serum FGF21 concentrations in MHO and MUHO subjects Data adjusted for gender, age, and BMI are shown as log-transformed individual data and means ± SD (N = 10 per group). Adjustment was performed by multiple linear regression modeling. MHO – metabolically healthy obesity; MUHO – metabolically unhealthy obesity.
Mentions: After adjustment for the putative confounders gender, age, and BMI by multiple linear regression modeling, serum FGF21 concentrations were more than twice as high in MUHO subjects as compared to MHO subjects (unadjusted 457 ± 378 vs. 211 ± 123 pg/mL, means ± SD; adjusted data presented in Figure 1; p = 0.023).

Bottom Line: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type-2 diabetes, and the metabolic syndrome.FGF21 treatment of human preadipocytes for the entire differentiation period was modestly lipogenic (+15%; p < 0.05), reduced the expression of key adipogenic transcription factors (PPARG and CEBPA, -15% and -40%, respectively; p < 0.01 both), reduced adiponectin expression (-20%; p < 0.05), markedly reduced adiponectin release (-60%; p < 0.01), and substantially increased leptin (+60%; p < 0.01) and interleukin-6 (+50%; p < 0.001) release.The hepatokine FGF21 exerts weak lipogenic and anti-adipogenic actions and marked adiponectin-suppressive and leptin and interleukin-6 release-promoting effects in human differentiating preadipocytes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Experimental Genetics, Helmholtz Centre Munich GmbH, German Research Centre for Environmental Health, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany ; German Centre for Diabetes Research (DZD), Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.

ABSTRACT

Objective: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type-2 diabetes, and the metabolic syndrome. We asked whether FGF21 levels differ between subjects with metabolically healthy vs. unhealthy obesity (MHO vs. MUHO), opening the possibility that FGF21 is a cross-talker between liver and adipose tissue in MUHO. Furthermore, we studied the effects of chronic FGF21 treatment on adipocyte differentiation, lipid storage, and adipokine secretion.

Methods: In 20 morbidly obese donors of abdominal subcutaneous fat biopsies discordant for their whole-body insulin sensitivity (hereby classified as MHO or MUHO subjects), serum FGF21 was quantified. The impact of chronic FGF21 treatment on differentiation, lipid accumulation, and adipokine release was assessed in isolated preadipocytes differentiated in vitro.

Results: Serum FGF21 concentrations were more than two-fold higher in MUHO as compared to MHO subjects (457 ± 378 vs. 211 ± 123 pg/mL; p < 0.05). FGF21 treatment of human preadipocytes for the entire differentiation period was modestly lipogenic (+15%; p < 0.05), reduced the expression of key adipogenic transcription factors (PPARG and CEBPA, -15% and -40%, respectively; p < 0.01 both), reduced adiponectin expression (-20%; p < 0.05), markedly reduced adiponectin release (-60%; p < 0.01), and substantially increased leptin (+60%; p < 0.01) and interleukin-6 (+50%; p < 0.001) release.

Conclusions: The hepatokine FGF21 exerts weak lipogenic and anti-adipogenic actions and marked adiponectin-suppressive and leptin and interleukin-6 release-promoting effects in human differentiating preadipocytes. Together with the higher serum concentrations in MUHO subjects, our findings reveal FGF21 as a circulating factor promoting the development of metabolically unhealthy adipocytes.

No MeSH data available.


Related in: MedlinePlus