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Conference Paper: Adipose tissue FGF21 resistance contributes to hypoadiponectinemia and insulin resistance in obesity: role of miR-34a

TitleAdipose tissue FGF21 resistance contributes to hypoadiponectinemia and insulin resistance in obesity: role of miR-34a
Authors
Lam, KSLChan, CYCStillitano, AWong, CMPang, YXu, A
Issue Date2015
Citation
The 75th Scientific Sessions of the American Diabetes Association (ADA 2015), Boston, MA., 5-9 June 2015. How to Cite?
AbstractFibroblast Growth Factor 21 (FGF21) is a hormone with beneficial effects on glucose and lipid homeostasis. We have previously reported its stimulatory effect on adiponectin secretion. However, serum FGF21 is paradoxically elevated in obesity and high FGF21 levels predict incident type 2 diabetes, suggesting that FGF21 resistance enhances the development of obesity-related type 2 diabetes. Here we sought to confirm the presence of FGF21 resistance in the adipose tissues of obese/overweight humans and investigate for the underlying mechanism. The expression levels of FGFR1, the receptor for FGF21, and β-klotho, its co-receptor protein, and miR-34a, were measured in visceral adipose tissues (VAT) collected during surgery from 24 overweight/obese (BMI > 23) Chinese women and 29 age- and sex-matched lean controls. To elucidate the effect of increased miR-34a on the expression of β-klotho, FGFR1 and adiponectin, 3T3-L1 pre-adipocytes were infected with lentiviral vector expressing miR-34a, before differentiation into mature adipocytes. Obese/overweight subjects had raised serum FGF21, reduced serum adiponectin, reduced VAT expressions of FGFR1 (all p<0.01) and β-klotho (p<0.05), but increased VAT expression of miR-34a (p<0.05), by RT-PCR. VAT FGFR1 and β-klotho expressions correlated inversely with the HOMA-IR insulin resistance index (both p<0.05), but positively with serum adiponectin (both p<0.01). On the other hand, VAT miR-34a expression correlated inversely with that of β-klotho, FGFR1 and adiponectin (all p<0.01), but positively with HOMA-IR (p<0.05). Lentivirus-mediated 5-fold increase in adipocyte miR-34a expression was accompanied by reduced β-klotho (p<0.01), FGFR1 (p<0.01) and adiponectin (p<0.001) expressions. We conclude that MiR-34a mediated FGF21 resistance is present in the adipose tissues of obese/overweight subjects and may contribute to obesity-related insulin resistance, in part via inducing hypoadiponectinaemia
DescriptionPoster Presentation: Insulin Action - Adipocyte Biology: no. 1866-P
Persistent Identifierhttp://hdl.handle.net/10722/217549

 

DC FieldValueLanguage
dc.contributor.authorLam, KSL-
dc.contributor.authorChan, CYC-
dc.contributor.authorStillitano, A-
dc.contributor.authorWong, CM-
dc.contributor.authorPang, Y-
dc.contributor.authorXu, A-
dc.date.accessioned2015-09-18T06:04:10Z-
dc.date.available2015-09-18T06:04:10Z-
dc.date.issued2015-
dc.identifier.citationThe 75th Scientific Sessions of the American Diabetes Association (ADA 2015), Boston, MA., 5-9 June 2015.-
dc.identifier.urihttp://hdl.handle.net/10722/217549-
dc.descriptionPoster Presentation: Insulin Action - Adipocyte Biology: no. 1866-P-
dc.description.abstractFibroblast Growth Factor 21 (FGF21) is a hormone with beneficial effects on glucose and lipid homeostasis. We have previously reported its stimulatory effect on adiponectin secretion. However, serum FGF21 is paradoxically elevated in obesity and high FGF21 levels predict incident type 2 diabetes, suggesting that FGF21 resistance enhances the development of obesity-related type 2 diabetes. Here we sought to confirm the presence of FGF21 resistance in the adipose tissues of obese/overweight humans and investigate for the underlying mechanism. The expression levels of FGFR1, the receptor for FGF21, and β-klotho, its co-receptor protein, and miR-34a, were measured in visceral adipose tissues (VAT) collected during surgery from 24 overweight/obese (BMI > 23) Chinese women and 29 age- and sex-matched lean controls. To elucidate the effect of increased miR-34a on the expression of β-klotho, FGFR1 and adiponectin, 3T3-L1 pre-adipocytes were infected with lentiviral vector expressing miR-34a, before differentiation into mature adipocytes. Obese/overweight subjects had raised serum FGF21, reduced serum adiponectin, reduced VAT expressions of FGFR1 (all p<0.01) and β-klotho (p<0.05), but increased VAT expression of miR-34a (p<0.05), by RT-PCR. VAT FGFR1 and β-klotho expressions correlated inversely with the HOMA-IR insulin resistance index (both p<0.05), but positively with serum adiponectin (both p<0.01). On the other hand, VAT miR-34a expression correlated inversely with that of β-klotho, FGFR1 and adiponectin (all p<0.01), but positively with HOMA-IR (p<0.05). Lentivirus-mediated 5-fold increase in adipocyte miR-34a expression was accompanied by reduced β-klotho (p<0.01), FGFR1 (p<0.01) and adiponectin (p<0.001) expressions. We conclude that MiR-34a mediated FGF21 resistance is present in the adipose tissues of obese/overweight subjects and may contribute to obesity-related insulin resistance, in part via inducing hypoadiponectinaemia-
dc.languageeng-
dc.relation.ispartofScientific Sessions of the American Diabetes Association, ADA 2015-
dc.titleAdipose tissue FGF21 resistance contributes to hypoadiponectinemia and insulin resistance in obesity: role of miR-34a-
dc.typeConference_Paper-
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.emailChan, CYC: yukchan@hku.hk-
dc.identifier.emailWong, CM: wispwong@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityLam, KSL=rp00343-
dc.identifier.authorityWong, CM=rp01489-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturepostprint-
dc.identifier.hkuros254456-

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