scholarly journals A common allele in FGF21 associated with preference for sugar consumption lowers body fat in the lower body and increases blood pressure

2017 ◽  
Author(s):  
Timothy M. Frayling ◽  
Robin N. Beaumont ◽  
Samuel E. Jones ◽  
Hanieh Yaghootkar ◽  
Marcus A. Tuke ◽  
...  

SummaryFibroblast Growth Factor 21 (FGF21) is a hormone that induces weight loss in model organisms. These findings have led to trials in humans of FGF21 analogues with some showing weight loss and lipid lowering effects. Recent genetic studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed but there was little evidence of an effect on metabolic traits. We studied a common FGF21 allele (A:rs838133) in 451,099 people from the UK Biobank study. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with body fat distribution, with less fat in the lower body, and higher blood pressure, than it is with BMI, where there is only nominal evidence of an effect. These human phenotypes of naturally occurring variation in the FGF21 gene will inform decisions about FGF21’s therapeutic potential.

1991 ◽  
Vol 9 (6) ◽  
pp. S441
Author(s):  
Bjorn Fagerberg ◽  
A. Berglund ◽  
Goran Berglund ◽  
Ove K. Andersson

1998 ◽  
Vol 83 (5) ◽  
pp. 1706-1712 ◽  
Author(s):  
Janneke G. Langendonk ◽  
Hanno Pijl ◽  
Arnoud C. Toornvliet ◽  
Jacobus Burggraaf ◽  
Marijke Frölich ◽  
...  

2015 ◽  
Vol 40 (7) ◽  
pp. 695-702 ◽  
Author(s):  
Eve Normandin ◽  
Eric Doucet ◽  
Rémi Rabasa-Lhoret ◽  
Martin Brochu

Obesity is a heterogeneous condition, since the metabolic profile may differ greatly from one individual to another. The objective of this study was to compare the effect of a 6-month diet-induced weight loss program on body composition and the metabolic profile in obese individuals displaying different obesity phenotypes. Secondary analyses were done on 129 obese (% body fat: 46% ± 4%) postmenopausal women (age: 57 ± 4 years). Outcome measures included body composition, body fat distribution, glucose homeostasis, fasting lipids, and blood pressure. Obesity phenotypes were determined based on lean body mass (LBM) index (LBMI = LBM/height2) and visceral fat (VF) accumulation, as follows: 1, lower VF and lower LBMI (n = 35); 2, lower VF and higher LBMI (n = 19); 3, higher VF and lower LBMI (n = 14); and 4, higher VF and higher LBMI (n = 61). All groups had significantly improved measures of body composition after the intervention (P < 0.0001). Greater decreases in LBM and LBMI were observed in the higher LBMI groups than in the lower LBMI groups (P < 0.0001). Similarly, decreases in VF were greater in the higher VF groups than in the lower VF groups (P < 0.05). Overall, fasting insulin levels and glucose disposal improved following the intervention, with higher LBMI groups showing a trend for greater improvements (P = 0.06 and 0.07, respectively). Overall, no difference was observed among the different obesity phenotypes regarding improvements in the metabolic profile in response to weight loss. Individuals displaying higher VF or higher LBMI at baseline experienced significantly greater decreases for these variables after the intervention.


2007 ◽  
Vol 292 (5) ◽  
pp. R1834-R1838 ◽  
Author(s):  
Christopher L. Gentile ◽  
Jeb S. Orr ◽  
Brenda M. Davy ◽  
Kevin P. Davy

We tested the hypothesis that modest, overfeeding-induced weight gain would increase sympathetic neural activity in nonobese humans. Twelve healthy males (23 ± 2 years; body mass index, 23.8 ± 0.7) were overfed ∼1,000 kcal/day until a 5-kg weight gain was achieved. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure, body composition (dual energy X-ray absorptiometry), and abdominal fat distribution (computed tomography) were measured at baseline and following 4 wk of weight stability at each individual's elevated body weight. Overfeeding increased body weight (73.5 ± 3.1 vs. 78.4 ± 3.2 kg, P < 0.001) and body fat (14.9 ± 1.2 vs. 18 ± 1.1 kg, P < 0.001) in 42 ± 8 days. Total abdominal fat increased (220 ± 22 vs. 266 ± 22 cm2, P < 0.001) with weight gain, due to increases in both subcutaneous (158 ± 15 vs. 187 ± 12 cm2, P < 0.001) and visceral fat (63 ± 8 vs. 79 ± 12 cm2, P = 0.004). As hypothesized, weight gain elicited increases in MSNA burst frequency (32 ± 2 vs. 38 ± 2 burst/min, P = 0.002) and burst incidence (52 ± 4 vs. 59 ± 3 bursts/100 heart beats, P = 0.026). Systolic, but not diastolic blood pressure increased significantly with weight gain. The change in MSNA burst frequency was correlated with the percent increase in body weight ( r = 0.59, P = 0.022), change in body fat ( r = 0.52, P = 0.043) and percent change in body fat ( r = 0.51, P = 0.045). The results of the current study indicate that modest diet-induced weight gain elicits sympathetic neural activation in nonobese males. These findings may have important implications for understanding the link between obesity and hypertension.


2009 ◽  
Vol 161 (6) ◽  
pp. 887-894 ◽  
Author(s):  
Jeanne Margot Kroese ◽  
Christiaan F Mooij ◽  
Marinette van der Graaf ◽  
Ad R M M Hermus ◽  
Cees J Tack

ContextPatients with congenital adrenal hyperplasia (CAH) are chronically treated with supraphysiological doses of glucocorticoids, which are known to induce insulin resistance. Thiazolidinediones might reverse this effect and improve insulin sensitivity.ObjectivesTo assess insulin sensitivity in CAH patients and the effect of pioglitazone treatment on insulin sensitivity in CAH patients. Secondary objectives were the effects of treatment with pioglitazone on blood pressure, body fat distribution, lipid, and steroid profiles.DesignRandomized placebo controlled crossover trial.ParticipantsTwelve CAH patients and 12 body mass and age-matched control subjects.InterventionSixteen-week treatment with pioglitazone (45 mg/day) or placebo.Main outcome measureInsulin sensitivity measured by euglycemic clamp and oral glucose tolerance test. Further measures were 24-h blood pressure profiles, body fat distribution measured by magnetic resonance imaging, dual energy x-ray absorptiometry (DEXA) and bioimpedance procedures, liver fat by magnetic resonance spectroscopy, lipid, and steroid profiles.ResultsCAH patients were insulin resistant compared with healthy controls. Treatment with pioglitazone significantly improved insulin sensitivity in CAH patients (glucose infusion rate (GIR) from 28.5±11.6 to 38.9±11.0 μmol/kg per min, P=0.000, GIR in controls 46.2±23.4 μmol/kg per min, P<0.05 versus CAH). Treatment with pioglitazone decreased blood pressure (systolic: 124.0±13.6 vs 127.0±14.9 mmHg, P<0.001, diastolic: 72.8±11.5 vs 77.4±12.6 mmHg, P<0.001). No changes in body fat distribution, lipid, and steroid profiles were observed.ConclusionsCAH patients are insulin resistant compared with matched control subjects. Treatment with pioglitazone improves insulin sensitivity and decreases blood pressure in CAH patients.


1990 ◽  
Vol 1 (1) ◽  
pp. 33-48 ◽  
Author(s):  
Patricia A Cassano ◽  
Mark R Segal ◽  
Pantel S Vokonas ◽  
Scott T Weiss

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