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Genetic variations in APPL2 are associated with overweight and obesity in a Chinese population with normal glucose tolerance.

ABSTRACT: BACKGROUND: APPL1 and APPL2 are two adaptor proteins, which can mediate adiponectin signaling via binding to N terminus of adiponectin receptors in muscle cells. Genes encoding adiponectin and adiponectin receptors contribute to insulin resistance and the risk of obesity, and genetic variants of APPL1 are associated with body fat distribution. However, the association between genetic variations of APPL2 and metabolic traits remains unknown. In the current study, we aimed to test the impacts of APPL2 genetic variants on obesity in a Chinese population with normal glucose tolerance. METHODS: We genotyped six single nucleotide polymorphisms (SNPs) in APPL2 in 1,808 non-diabetic subjects. Overweight and obesity were defined by body mass index (BMI). Obesity-related anthropometric parameters were measured, including height, weight, waist circumference, hip circumference. BMI and waist-hip ratio (WHR) were calculated. RESULTS: We found significant evidence of association with overweight/obesity for rs2272495 and rs1107756. rs2272495 C allele and rs1107756 T allele both conferred a higher risk of being overweight and obese (OR 1.218, 95% CI 1.047-1.416, p = 0.011 for rs2272495; OR 1.166, 95% CI 1.014-1.341, p = 0.031 for rs1107756). After adjusting multiple comparisons, only the effect of rs2272495 on overweight/obesity remained to be significant (empirical p = 0.043). Moreover, we investigated the effects of these SNPs on obesity-related quantitative traits in all participants. rs2272495 was associated with BMI (p = 0.015), waist circumference (p = 0.006), hip circumference (p = 0.025) as well as WHR (p = 0.047) under a recessive model. Similar associations were found for rs1107756 except for WHR. CONCLUSION: This study suggests that genetic variations in APPL2 are associated with overweight and obesity in Chinese population with normal glucose tolerance.

SUBMITTER: Jiang S

PROVIDER: S-EPMC3368742 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Genetic variations in APPL2 are associated with overweight and obesity in a Chinese population with normal glucose tolerance.

Jiang Shan S Fang Qichen Q Yu Weihui W Zhang Rong R Hu Cheng C Dong Kun K Bao Yuqian Y Wang Chen C Xiang Kunsan K Jia Weiping W

BMC medical genetics 20120330

<h4>Background</h4>APPL1 and APPL2 are two adaptor proteins, which can mediate adiponectin signaling via binding to N terminus of adiponectin receptors in muscle cells. Genes encoding adiponectin and adiponectin receptors contribute to insulin resistance and the risk of obesity, and genetic variants of APPL1 are associated with body fat distribution. However, the association between genetic variations of APPL2 and metabolic traits remains unknown. In the current study, we aimed to test the impac ...[more]

PMID: 22462604

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Project description:BackgroundAlthough intake of Hass avocado has been cross-sectionally linked to lower abdominal obesity, knowledge of the effects of avocado consumption on abdominal adiposity and glycemic outcomes remains limited.ObjectiveThe effects of avocado consumption on abdominal adiposity, insulin resistance, oral-glucose-tolerance test (OGTT), and estimated β-cell function were evaluated.MethodsA total of 105 adults aged 25-45 y (61% female) with BMI ≥25 kg/m2 were randomly assigned to an intervention (N = 53) that received a daily meal with 1 fresh Hass avocado or a control (N = 52) that received an isocaloric meal with similar ingredients without avocado for 12 wk. DXA was used to assess the primary outcomes of abdominal adiposity [visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and the ratio of VAT to SAAT (VS Ratio)]. Fasted glucose and insulin were used to assess the primary outcomes of insulin resistance (HOMA-IR), and insulin sensitivity (Matsuda index) and β-cell function (Insulinogenic index) were estimated using an OGTT. Changes between groups were compared using an ANCOVA. Secondary analyses were conducted based on sex.ResultsThe control group exhibited a greater reduction in SAAT [-54.5 ± 155.8 g (control) compared with 17.4 ± 155.1 g (treatment), P = 0.017] and increase in VS Ratio [0.007 ± 0.047 (control) compared with -0.011 ± 0.044 (treatment), P = 0.024]. Among females, the treatment group exhibited a greater reduction in VAT [1.6 ± 89.8 g (control) compared with -32.9 ± 81.6 g (treatment), P = 0.021] and VS Ratio [0.01 ± 0.05 (control) compared with -0.01 ± 0.03 (treatment), P = 0.001]. Among males, there was no significant difference between groups in changes in abdominal adiposity or glycemic outcomes.ConclusionsDaily consumption of 1 fresh Hass avocado changed abdominal adiposity distribution among females but did not facilitate improvements in peripheral insulin sensitivity or β-cell function among adults with overweight and obesity.This study was registered at clinicaltrials.gov as NCT02740439.

Project description:Betatrophin may increase islet β cell proliferation in insulin resistance and irisin may improve glucose tolerance in mice. To examine the relationship between betatrophin and irisin, we investigated it in middle-aged Chinese subjects with normal glucose tolerance (NGT) and type 2 diabetes mellitus (T2DM).A total of 460 permanent residents of Fengxian District, aged 40-60 years and without T2DM, were enrolled. Anthropometric parameters, oral glucose tolerance test (OGTT) results, glycosylated haemoglobin levels, blood lipid levels, insulin sensitivity (homeostasis model assessment of insulin resistance, HOMA-IR), β cell function (homeostasis model assessment-β, HOMA-β), estimated glomerular filtration rate (eGFR) and body fat composition were determined. Matched for age, gender and body mass index (BMI, 18-28 kg/m2), newly diagnosed T2DM (n = 50, male/female = 23/27) and NGT (n = 50, male/female = 21/29) subjects were selected based on the results of an OGTT. Serum betatrophin and irisin levels were determined by enzyme linked immune sorbent assay (ELISA).Males had higher levels of betatrophin compared with females in both the NGT and T2DM groups. Compared with NGT subjects, the level of betatrophin in the T2DM group was higher, and males in the T2DM group had higher betatrophin levels than males in the NGT group, but there was no significant difference in betatrophin levels in females between the T2DM and NGT groups. Spearman's correlation analysis revealed that serum betatrophin levels in females with NGT were positively correlated with irisin and negatively correlated with FINS (fasting insulin) levels ( p < 0.05), but no correlation was found between betatrophin and irisin levels in males with NGT or in males or females with T2DM. In females with T2DM, circulating betatrophin levels were positively correlated with weight, BMI and hip circumference (p < 0.05) but negatively correlated with FPG (fasting plasma glucose) and HOMA-IR (p < 0.05).Gender differences in the relationship between betatrophin and irisin indicate that there might be cytokine-mediated crosstalk among the liver, adipose tissue and skeletal muscle.

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Genetic variations in APPL2 are associated with overweight and obesity in a Chinese population with normal glucose tolerance.

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Genetic variations in APPL2 are associated with overweight and obesity in a Chinese population with normal glucose tolerance.

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