Impaired hypothalamic Fto expression in response to fasting and glucose in obese mice

Poritsanos, Nicole J.; Lew, Pei San; Fischer, Julia; Mobbs, Charles V.; Nagy, J.I.; Wong, Davie; Rüther, Ulrich; Mizuno, Tooru M.

doi:10.1038/nutd.2011.15

Cited by 42 publications

(32 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, AA genotypes demonstrated a 0.32-fold decrease in FTO mRNA expression compared to a 0.21-fold and 0.11-fold decrease for AT and TT genotypes respectively, at 10 min post-exercise. Previous studies have shown that FTO gene activity is nutritionally regulated with high fat diet, fasting and glucose ingestion all having effects on FTO mRNA levels [26][27][28]. Only one other study has investigated the effect of high intensity training on FTO mRNA expression and showed lifestyle changes (diet and exercise) did not impact FTO gene expression in peripheral blood mononuclear cells [29].…”

Section: Discussionmentioning

confidence: 99%

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females

et al. 2020

View full text Add to dashboard Cite

Background: Physical exercise and activity status may modify the effect of the fat mass-and obesity-associated (FTO) genotype on body weight and obesity risk. To understand the interaction between FTO's effect and physical activity, the present study investigated the effects of high and low intensity exercise on FTO mRNA and protein expression, and potential modifiers of exercise-induced changes in FTO in healthy-weighted individuals. Methods: Twenty-eight untrained males and females (25.4 ± 1.1 years; 73.1 ± 2.0 kg; 178.8 ± 1.4 cm; 39.0 ± 1.2 ml.kg.min − 1 VO 2peak) were genotyped for the FTO rs9939609 (T > A) polymorphism and performed isocaloric (400 kcal) cycle ergometer exercise on two separate occasions at different intensities: 80% (High Intensity (HI)) and 40% (Low Intensity (LO)) VO 2peak. Skeletal muscle biopsies (vastus lateralis) and blood samples were taken pre-exercise and following 10 and 90 mins passive recovery. Results: FTO mRNA expression was significantly decreased after HI intensity exercise (p = 0.003). No differences in basal and post-exercise FTO protein expression were evident between FTO genotypes. Phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) were significantly increased following HI intensity exercise (p < 0.05). Multivariate models of metabolomic data (orthogonal two partial least squares discriminant analysis (O2PLS-DA)) were unable to detect any significant metabolic differences between genotypes with either exercise trial (p > 0.05). However, skeletal muscle glucose accumulation at 10 mins following HI (p = 0.021) and LO (p = 0.033) intensity exercise was greater in AA genotypes compared to TT genotypes. Conclusion: Our novel data provides preliminary evidence regarding the effects of exercise on FTO expression in skeletal muscle. Specifically, high intensity exercise downregulates expression of FTO mRNA and suggests that in addition to nutritional regulation, FTO could also be regulated by exercise. Trial registration: ACTRN12612001230842. Registered

show abstract

Section: Discussionmentioning

confidence: 99%

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females

et al. 2020

View full text Add to dashboard Cite

show abstract

“…However, that the results of recent studies on the effect of dietary macronutrients on FTO and IRX3 gene expression were inconsistent. In regards to dietary carbohydrate, Poritsano et al reported that higher carbohydrate especially glucose intake up-regulated FTO gene expression [21]. On the other hand, Boender et al found that increased sucrose administration reduced FTO gene expression [22].…”

Section: Discussionmentioning

confidence: 99%

Interactions between macro-nutrients’ intake, FTO and IRX3 gene expression, and FTO genotype in obese and overweight male adolescents

et al. 2019

View full text Add to dashboard Cite

This study is the first to identify the effects of FTO genotype on the interactions between the level of macro-nutrients intake and the expression level of fat mass and obesity associated (FTO) and homeobox transcription factor iriquois-3 (IRX3) genes This longitudinal study was carried out on 84 overweight and obese adolescent boys in Tehran, Iran. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in PBMCs and macro-nutrients' intake were assessed at baseline and after 18 weeks of the intervention. The results identified that the higher carbohydrates intake significantly up-regulated the FTO gene (P = 0.001) and down-regulated the IRX3 gene (P = 0.01). Protein intake up-regulated the FTO gene (P = 0.001). In carriers of GG genotype of FTO gene, the amount of dietary carbohydrate had a positive association with FTO gene expression (p = 0.001, and p = 0.04, respectively). In AA/AG carriers, dietary protein was positively associated with FTO gene expression (p = 0.001) and dietary carbohydrate was negatively associated with IRX3 gene expression (P = 0.04). Therefore, dietary carbohydrateseems to be associated with FTO and IRX3 genes expression. These associations are influenced by FTO genotype.

show abstract

“…NFκB and its upstream regulator IKKb, are both expressed abundantly in the medial basal hypothalamus, remain suppressed under chow conditions and are activated by states of over-nutrition, including HFD and acute central overload of fatty acid and glucose [18]. This mirrors the nutritional regulation of Fto mRNA within the medial basal hypothalamus; being down-regulated by fasting [4,14,15] and up-regulated by feeding [42] and a HFD [15], [16].…”

Section: Discussionmentioning

confidence: 99%

FTO is necessary for the induction of leptin resistance by high-fat feeding

Tung

Gulati

Liu

et al. 2015

Molecular Metabolism

View full text Add to dashboard Cite

ObjectiveLoss of function FTO mutations significantly impact body composition in humans and mice, with Fto-deficient mice reported to resist the development of obesity in response to a high-fat diet (HFD). We aimed to further explore the interactions between FTO and HFD and determine if FTO can influence the adverse metabolic consequence of HFD.MethodsWe studied mice deficient in FTO in two well validated models of leptin resistance (HFD feeding and central palmitate injection) to determine how Fto genotype may influence the action of leptin. Using transcriptomic analysis of hypothalamic tissue to identify relevant pathways affected by the loss of Fto, we combined data from co-immunoprecipitation, yeast 2-hybrid and luciferase reporter assays to identify mechanisms through which FTO can influence the development of leptin resistant states.ResultsMice deficient in Fto significantly increased their fat mass in response to HFD. Fto+/− and Fto−/− mice remained sensitive to the anorexigenic effects of leptin, both after exposure to a HFD or after acute central application of palmitate. Genes encoding components of the NFкB signalling pathway were down-regulated in the hypothalami of Fto-deficient mice following a HFD. When this pathway was reactivated in Fto-deficient mice with a single low central dose of TNFα, the mice became less sensitive to the effect of leptin. We identified a transcriptional coactivator of NFкB, TRIP4, as a binding partner of FTO and a molecule that is required for TRIP4 dependent transactivation of NFкB.ConclusionsOur study demonstrates that, independent of body weight, Fto influences the metabolic outcomes of a HFD through alteration of hypothalamic NFкB signalling. This supports the notion that pharmacological modulation of FTO activity might have the potential for therapeutic benefit in improving leptin sensitivity, in a manner that is influenced by the nutritional environment.

show abstract

Impaired hypothalamic Fto expression in response to fasting and glucose in obese mice

Cited by 42 publications

References 47 publications

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females

Interactions between macro-nutrients’ intake, FTO and IRX3 gene expression, and FTO genotype in obese and overweight male adolescents

FTO is necessary for the induction of leptin resistance by high-fat feeding

Contact Info

Product

Resources

About