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

Klöting, Nora; Schleinitz, Dorit; Ruschke, Karen; Berndt, Janin; Faßhauer, Mathias; Tönjes, Anke; Schön, Michael P.; Kovacs, Peter; Stümvoll, Michael; Blüher, Matthias

doi:10.1007/s00125-008-0928-9

Cited by 98 publications

(97 citation statements)

References 19 publications

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“…To date, only a few studies have examined FTO gene expression in paired OAT and SAT and discordant results were reported. Some studies found no site-specific difference (20)(21)(22)33), while another study found a threefold higher FTO expression in SAT compared to visceral adipose tissue (16). The discrepancy of our results with these studies is difficult to interpret, but it is worth noting that our population included women exclusively, and covered the lean to moderately obese range while other studies reporting no difference were performed mostly in severely obese patients of both sexes.…”

Section: Figure 4 Effect Of Fto Silencing On 3t3-l1 Differentiation contrasting

confidence: 89%

“…However, the function of FTO and its role in human obesity and T2D remains to be defined. In particular, the association of FTO expression in adipose tissue with fat depot and with obesity still remains controversial in humans (16,(20)(21)(22)33). In addition, very few studies have investigated the relationship between FTO expression in adipose tissue and insulin sensitivity (18,21).…”

Section: Discussionmentioning

confidence: 99%

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The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity

Bravard

Veilleux

Disse

et al. 2013

Obesity

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Objective: The fat mass and obesity associated (FTO) gene is related to obesity, but the regulation of FTO expression in adipose tissue is not fully understood. We investigated FTO expression in paired subcutaneous and omental adipose tissues (SAT and OAT) from healthy women undergoing gynecological surgeries, and its relation with adiposity and insulin sensitivity. Design and Methods: FTO expression in SAT of type 2 diabetic patients treated or not with Rosiglitazone was also compared. Results: Both the mRNA and protein levels of FTO were higher in OAT from women than in SAT. Only OAT FTO protein levels negatively correlated with BMI and body fat mass, whereas SAT FTO mRNA levels were negatively correlated with subcutaneous fat deposition. In addition, SAT FTO mRNA and protein levels were increased in insulin resistant women (high HOMA) compared to insulin sensitive women (low HOMA), whereas OAT FTO expression was not different between these two subgroups. Interestingly, FTO mRNA levels were increased in SAT of type 2 diabetic patients, and treatment of diabetics with Rosiglitazone improved insulin sensitivity and reduced SAT FTO mRNA levels. Lastly, FTO expression was transiently increased in the early phase of 3T3-L1 cell differentiation, which coincides with the induction of PPARc2 expression. However, partial reduction of FTO did not impact PPARc2 expression and adipocyte differentiation. Conclusion: Therefore, FTO gene expression is higher in OAT than in SAT in lean to moderately obese women. OAT FTO expression is associated with adiposity, whereas SAT FTO expression is associated with insulin sensitivity. These associations are independent of an effect of FTO on adipocyte differentiation.

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Section: Figure 4 Effect Of Fto Silencing On 3t3-l1 Differentiation contrasting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity

Bravard

Veilleux

Disse

et al. 2013

Obesity

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“…Cohort 2. Adipose tissue progranulin mRNA and protein expression was investigated in 55 previously described donors of paired omental and subcutaneous adipose tissue samples (20), who underwent open abdominal surgery for cholecystectomy, weight reduction surgery, abdominal injuries, or explorative laparotomy. All subjects had a stable weight, defined as the absence of fluctuations of Ͼ2% of body weight for at least 3 months before surgery.…”

Section: Methodsmentioning

confidence: 99%

Serum Progranulin Concentrations May Be Associated With Macrophage Infiltration Into Omental Adipose Tissue

et al. 2009

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OBJECTIVE-Progranulin is an important molecule in inflammatory response. Chronic inflammation is frequently associated with central obesity and associated disturbances; however, the role of circulating progranulin in human obesity, type 2 diabetes, and dyslipidemia is unknown.RESEARCH DESIGN AND METHODS-For the measurement of progranulin serum concentrations, we developed an enzymelinked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating progranulin in a cross-sectional study of 209 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal (NGT) or impaired (IGT) glucose tolerance or type 2 diabetes before and after a 4-week physical training program. Progranulin mRNA and protein expression was measured in paired samples of omental and subcutaneous adipose tissue (adipocytes and cells of the stromal vascular fraction) from 55 lean or obese individuals. Measurement of Erk activation and chemotactic activity induced by progranulin in vitro was performed using THP-1-based cell migration assays.RESULTS-Progranulin serum concentrations were significantly higher in individuals with type 2 diabetes compared with NGT and in obese subjects with predominant visceral fat accumulation. Circulating progranulin significantly correlates with BMI, macrophage infiltration in omental adipose tissue, C-reactive protein (CRP) serum concentrations, A1C values, and total cholesterol. Multivariable linear regression analyses revealed CRP levels as the strongest independent predictor of circulating progranulin. The extent of in vitro progranulin-mediated chemotaxis is similar to that of monocyte chemoattractant protein-1 but independent of G␣. Moreover, in type 2 diabetes, but not in IGT and NGT individuals, physical training for 4 weeks resulted in significantly decreased circulating progranulin levels.CONCLUSIONS-Elevated progranulin serum concentrations are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. We identified progranulin as a novel marker of chronic inflammation in obesity and type 2 diabetes that closely reflects omental adipose tissue macrophage infiltration. Physical training significantly reduces elevated circulating progranulin in patients with type 2 diabetes. Diabetes 58:627-636, 2009

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“…Results from human studies further indicate that FTO gene expression in adipocytes can be upregulated in obesity (Kloting et al 2008), an adaptation dependent on duration and severity. In our ovine model, we found a trend for a similar response in perirenal adipose tissue, suggesting that with an extended period of obesity the same adaptation would occur.…”

Section: Obesity-related Alterationsmentioning

confidence: 97%

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

Sebért¹,

Hyatt²,

Chan³

et al. 2010

Reproduction

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The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary 'Western' lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity.

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

Cited by 98 publications

References 19 publications

The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity

The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity

Serum Progranulin Concentrations May Be Associated With Macrophage Infiltration Into Omental Adipose Tissue

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

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