Skip to main content
Top
Published in: Diabetologia 4/2008

01-04-2008 | Article

Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans

Authors: N. Klöting, D. Schleinitz, K. Ruschke, J. Berndt, M. Fasshauer, A. Tönjes, M. R. Schön, P. Kovacs, M. Stumvoll, M. Blüher

Published in: Diabetologia | Issue 4/2008

Login to get access

Abstract

Aims/hypothesis

Recently, FTO was identified as a candidate gene contributing to both childhood and severe adult obesity. We tested the hypothesis that mRNA expression of FTO and/or of the neighbouring RPGRIP1L in adipose tissue correlates with measures of obesity and fat distribution. We also investigated whether the FTO obesity risk alleles might explain variability in FTO and RPGRIP1L mRNA expression.

Methods

In paired samples of visceral and subcutaneous adipose tissue from 55 lean and obese participants, we investigated whether FTO and RPGRIP1L mRNA expression is fat depot-specific, altered in obesity and related to measures of fat accumulation, insulin sensitivity and glucose metabolism. All participants were genotyped for the obesity-associated rs8050136 FTO variant.

Results

FTO mRNA expression was threefold higher in subcutaneous than in visceral adipose tissue. Subcutaneous FTO expression correlated with visceral FTO expression. FTO gene expression in both depots correlated with age and was negatively correlated to BMI and per cent body fat. FTO mRNA levels were not related to measures of insulin sensitivity and glucose metabolism. RPGRIP1L mRNA expression was 1.6-fold higher in visceral than in subcutaneous adipose tissue, but did not correlate with anthropometric and metabolic characteristics. There was no association between rs8050136 and FTO or RPGRIP1L mRNA expression in adipose tissue.

Conclusions/interpretation

Expression of adipose tissue FTO mRNA is fat depot-specific and negatively correlates with measures of obesity. However, the direction of this relationship still needs to be elucidated.
Literature
1.
go back to reference Maes HH, Neale MC, Eaves LJ (1997) Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 27:325–351PubMedCrossRef Maes HH, Neale MC, Eaves LJ (1997) Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 27:325–351PubMedCrossRef
3.
go back to reference Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894PubMedCrossRef Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894PubMedCrossRef
4.
go back to reference Dina C, Meyre D, Gallina S et al (2007) Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 39:724–726PubMedCrossRef Dina C, Meyre D, Gallina S et al (2007) Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 39:724–726PubMedCrossRef
5.
go back to reference Scuteri A, Sanna S, Chen WM et al (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3:e115PubMedCrossRef Scuteri A, Sanna S, Chen WM et al (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3:e115PubMedCrossRef
6.
go back to reference van der Hoeven F, Schimmang T, Volkmann A, Mattei MG, Kyewski B, Ruther U (1994) Programmed cell death is affected in the novel mouse mutant Fused toes (Ft). Development 120:2601–2607PubMed van der Hoeven F, Schimmang T, Volkmann A, Mattei MG, Kyewski B, Ruther U (1994) Programmed cell death is affected in the novel mouse mutant Fused toes (Ft). Development 120:2601–2607PubMed
7.
go back to reference Peters T, Ausmeier K, Ruther U (1999) Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation. Mamm Genome 10:983–986PubMedCrossRef Peters T, Ausmeier K, Ruther U (1999) Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation. Mamm Genome 10:983–986PubMedCrossRef
8.
go back to reference Stratakis CA, Lafferty A, Taymans SE, Gafni RI, Meck JM, Blancato J (2000) Anisomastia associated with interstitial duplication of chromosome 16, mental retardation, obesity, dysmorphic facies, and digital anomalies: molecular mapping of a new syndrome by fluorescent in situ hybridization and microsatellites to 16q13 (D16S419–D16S503). J Clin Endocrinol Metab 85:3396–3401PubMedCrossRef Stratakis CA, Lafferty A, Taymans SE, Gafni RI, Meck JM, Blancato J (2000) Anisomastia associated with interstitial duplication of chromosome 16, mental retardation, obesity, dysmorphic facies, and digital anomalies: molecular mapping of a new syndrome by fluorescent in situ hybridization and microsatellites to 16q13 (D16S419–D16S503). J Clin Endocrinol Metab 85:3396–3401PubMedCrossRef
9.
go back to reference Gerken T, Girard CA, Tung YC et al (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318:1469–1472PubMedCrossRef Gerken T, Girard CA, Tung YC et al (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318:1469–1472PubMedCrossRef
10.
go back to reference DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:214–223 DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:214–223
11.
go back to reference Berndt J, Klöting N, Kralisch S et al (2005) Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes 54:2911–2916PubMedCrossRef Berndt J, Klöting N, Kralisch S et al (2005) Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes 54:2911–2916PubMedCrossRef
12.
go back to reference Klöting N, Graham TE, Berndt J et al (2007) Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab 6:79–87PubMedCrossRef Klöting N, Graham TE, Berndt J et al (2007) Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab 6:79–87PubMedCrossRef
13.
go back to reference Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738PubMedCrossRef Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738PubMedCrossRef
14.
go back to reference Frayn KN (2000) Visceral fat and insulin resistance–causative or correlative? Br J Nutr 83:S71–S77PubMedCrossRef Frayn KN (2000) Visceral fat and insulin resistance–causative or correlative? Br J Nutr 83:S71–S77PubMedCrossRef
15.
go back to reference Klein S, Fontana L, Young VL et al (2004) Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 350:2549–2557PubMedCrossRef Klein S, Fontana L, Young VL et al (2004) Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 350:2549–2557PubMedCrossRef
16.
go back to reference Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P (2002) A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord 26:193–199PubMedCrossRef Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P (2002) A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord 26:193–199PubMedCrossRef
17.
go back to reference Delous M, Baala L, Salomon R et al (2007) The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet 39:875–881PubMedCrossRef Delous M, Baala L, Salomon R et al (2007) The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet 39:875–881PubMedCrossRef
18.
go back to reference Arts HH, Doherty D, van Beersum SEC et al (2007) Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome. Nat Genet 39:882–888PubMedCrossRef Arts HH, Doherty D, van Beersum SEC et al (2007) Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome. Nat Genet 39:882–888PubMedCrossRef
Metadata
Title
Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans
Authors
N. Klöting
D. Schleinitz
K. Ruschke
J. Berndt
M. Fasshauer
A. Tönjes
M. R. Schön
P. Kovacs
M. Stumvoll
M. Blüher
Publication date
01-04-2008
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 4/2008
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-008-0928-9

Other articles of this Issue 4/2008

Diabetologia 4/2008 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.