Obesity is a major health problem, especially in populations with an increasing imbalance between energy intake and expenditure. The health problems associated with obesity are numerous and range from an increased risk for developing type 2 diabetes to certain types of cancer. Recent evidence suggests a key role for the brain in controlling both body fat content and glucose metabolism (1). Leptin, an adipocyte-secreted hormone, acts on different neurons in the hypothalamus, which ultimately results in inhibition of food intake and an increase in energy expenditure. Leptin levels increase in proportion to adiposity, however, most obese individuals become leptin-resistant (2,3).Targeting molecules involved in the development of leptin resistance is a potentially powerful therapeutic approach for combating the obesity epidemic. One such target could be the protein tyrosine phosphatase 1B (PTP1B) encoded by the protein tyrosine phosphatase nonreceptor type1 (PTPN1) gene. PTP1B interferes with the leptin pathway as well as with insulin signaling through actions in the brain. PTP1B suppresses the signaling pathway of leptin and increased activity of PTP1B leads to increased stimulation of food intake (1,4). Hence, variations of the PTPN1 gene may lead to changes in leptin sensitivity and thereby influence eating behavior and measures of obesity.Several studies (5-9) found an association between singlenucleotide polymorphisms (SNPs) in the PTPN1 gene and various measures of obesity, such as central fat, moderate obesity, BMI, and adiposity. However, each study analyzed the measures of obesity differently. For instance, defined obesity as BMI >40 kg/m 2 , whereas others defined obesity as BMI >30 kg/m 2 (5) or analyzed it as a continuous trait (7-9). This makes it hard to compare results from the different studies.So far no studies have been performed on the relation between the PTPN1 gene and macronutrient intake, the amount of visceral fat, or the difference between visceral and subcutaneous fat. The amount of macronutrient intake is important for the development of obesity (10-12), whereas visceral fat is the type of fat that is causing most harm (13).In this study, we investigated the association between four tag SNPs in the PTPN1 gene with macronutrient intake and different measures of obesity, including visceral fat.
ResultsTyping of the four tag SNPs resulted in genotype success rates between 95.8 and 98.4%. None of the SNPs deviated significantly from Hardy-Weinberg equilibrium (P > 0.05). Anthropometrical and food intake characteristics of the participants are shown in Table 1.Results of the linear regression analyses of nine dietary phenotypes with PTPN1 tag SNPs are shown in Tables 2,3 The protein tyrosine phosphatase nonreceptor type1 (PTPN1) gene encodes for the protein tyrosine phosphatase 1B, which suppresses the signaling pathway of leptin. Variations of the PTPN1 gene may lead to changes in leptin sensitivity and thereby influence eating behavior and measures of obesity. This study investigated the ass...
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