Jennifer Shea

Comparison of the Classification of Obesity by BMI vs. Dual-energy X-ray Absorptiometry in the Newfoundland Population

Although BMI is the most widely used measure of obesity, debate still exists on how accurately BMI defines obesity. In this study, adiposity status defined by BMI and dual‐energy X‐ray absorptiometry (DXA) was compared in a large population to evaluate the accuracy of BMI. A total of 1,691 adult volunteers from Newfoundland and Labrador participated in the study. BMI and body fat percentage (%BF) were measured for all subjects following a 12‐h fasting period. Subjects were categorized as underweight (UW), normal weight (NW), overweight (OW), or obese (OB) based on BMI and %BF criteria. Differences between the two methods were compared within gender and by age‐groups. According to BMI criteria, 1.2% of women were classified as UW, 44.2% as NW, 34.2% as OW, and 20.3% as OB. When women were classified according to %BF criteria, 2.2% were UW, 29.6% were NW, 30.9% were OW, and 37.1% were OB. The overall discrepancy between the two methods for women was substantial at 34.7% (14.6% for NW and 16.8% for OB, P < 0.001). In men, the overall discrepancy was 35.2% between BMI and DXA (17.6% for OW and 13.5% for OB, P < 0.001). Misclassification by BMI was dependent on age, gender, and adiposity status. In conclusion, BMI misclassified adiposity status in approximately one‐third of women and men compared with DXA. Caution should be taken when BMI is used in clinical and scientific research as well as clinical practice.

The Prevalence of Metabolically Healthy Obese Subjects Defined by BMI and Dual-Energy X-Ray Absorptiometry

Nearly one‐third of obese (OB) people are reported to be metabolically healthy based on BMI criteria. It is unknown whether this holds true when more accurate adiposity measurements are applied such as dual‐energy X‐ray absorptiometry (DXA). We compared differences in the prevalence of cardiometabolic abnormalities among adiposity groups classified using BMI vs. DXA criteria. A total of 1,907 adult volunteers from Newfoundland and Labrador participated. BMI and body fat percentage (%BF; measured using DXA) were measured following a 12‐h fasting period. Subjects were categorized as normal weight (NW), overweight (OW), or OB based on BMI and %BF criteria. Cardiometabolic abnormalities considered included elevated triglyceride, glucose, and high‐sensitivity C‐reactive protein (hsCRP) levels, decreased high‐density lipoprotein (HDL) cholesterol levels, insulin resistance, and hypertension. Subjects were classified as metabolically healthy (0 or 1 cardiometabolic abnormality) or abnormal (≥2 cardiometabolic abnormalities). We found low agreement in the prevalence of cardiometabolic abnormalities between BMI and %BF classifications (κ = 0.373, P < 0.001). Among NW and OW subjects, the prevalence of metabolically healthy individuals was similar between BMI and %BF (77.6 vs. 75.7% and 58.8 vs. 62.5%, respectively) however, there was a pronounced difference among OB subjects (34.0 vs. 47.7%, P < 0.05). Similar trends were evident using three additional definitions to characterize metabolically healthy individuals. Our findings indicate that approximately one‐half of OB people are metabolically healthy when classified using %BF criteria which is significantly higher than previously reported using BMI. Caution should therefore be taken when making inferences about the metabolic health of an OB population depending on the method used to measure adiposity.

High Dietary Magnesium Intake Is Associated with Low Insulin Resistance in the Newfoundland Population

Background Magnesium plays a role in glucose and insulin homeostasis and evidence suggests that magnesium intake is associated with insulin resistance (IR). However, data is inconsistent and most studies have not adequately controlled for critical confounding factors. Objective The study investigated the association between magnesium intake and IR in normal-weight (NW), overweight (OW) and obese (OB) along with pre- and post- menopausal women. Design A total of 2295 subjects (590 men and 1705 women) were recruited from the CODING study. Dietary magnesium intake was computed from the Willett Food Frequency Questionnaire (FFQ). Adiposity (NW, OW and OB) was classified by body fat percentage (%BF) measured by Dual-energy X-ray absorptiometry according to the Bray criteria. Multiple regression analyses were used to test adiposity-specific associations of dietary magnesium intake on insulin resistance adjusting for caloric intake, physical activity, medication use and menopausal status. Results Subjects with the highest intakes of dietary magnesium had the lowest levels of circulating insulin, HOMA-IR, and HOMA-ß and subjects with the lowest intake of dietary magnesium had the highest levels of these measures, suggesting a dose effect. Multiple regression analysis revealed a strong inverse association between dietary magnesium with IR. In addition, adiposity and menopausal status were found to be critical factors revealing that the association between dietary magnesium and IR was stronger in OW and OB along with Pre-menopausal women. Conclusion The results of this study indicate that higher dietary magnesium intake is strongly associated with the attenuation of insulin resistance and is more beneficial for overweight and obese individuals in the general population and pre-menopausal women. Moreover, the inverse correlation between insulin resistance and dietary magnesium intake is stronger when adjusting for %BF than BMI.

Changes in the transcriptome of abdominal subcutaneous adipose tissue in response to short-term overfeeding in lean and obese men

BACKGROUND Obesity is caused by the excessive accumulation of adipose tissue as a result of a chronic energy surplus. Little is known regarding the molecular mechanisms involved in the response to an energy surplus in human adipose tissue at the genomic level. OBJECTIVE The objective was to investigate changes in the transcriptome of abdominal subcutaneous adipose tissue after a positive energy challenge induced by overfeeding in both lean and obese subjects to identify novel obesity candidate genes. DESIGN A total of 26 men were recruited and classified on the basis of percentage body fat (measured by dual-energy X-ray absorptiometry) as lean (<20%) or obese (>25%) to participate in the baseline comparison. Sixteen men participated in the overfeeding study (8 lean and 8 obese). Adipose tissue biopsy samples were collected from all subjects at the subumbilical region. Global gene expression profiles were determined at baseline and after a 7-d hypercaloric diet at 40% above normal energy requirements by using whole human genome DNA microarrays. RESULTS Overfeeding induced differential expression in 45 genes. Six genes displayed a significant interaction effect between adiposity status and overfeeding treatment, including transferrin (TF), stearoyl-CoA desaturase (SCD), transaldolase 1 (TALDO1), cathepsin C (CTSC), insulin receptor substrate 2 (IRS2), and pyruvate dehydrogenase kinase, isozyme 4 (PDK4). Overfeeding resulted in changes in expression of these genes in lean subjects, whereas no significant changes were evident in obese subjects. CONCLUSIONS Differential expression of these 6 genes may represent a protective mechanism at the molecular level in lean subjects in response to an energy surplus. These genes represent valuable candidates for downstream studies related to obesity.

Serum peptide YY in response to short-term overfeeding in young men

BACKGROUND Peptide YY (PYY), a gut hormone that inhibits appetite, has been linked to the development of obesity. OBJECTIVE This study investigated the nutritional regulation of PYY after 7 d of overfeeding (70% above normal energy requirements) in normal-weight, overweight, and obese men. DESIGN Sixty-nine men (aged 19-29 y) participated in the study. We analyzed the relation between fasting serum PYY before and after a 7-d overfeeding challenge in normal-weight, overweight, and obese men. In addition, we analyzed PYY with obesity-related phenotypes including weight, percentage body fat (measured by dual-energy X-ray absorptiometry), body mass index (BMI), total cholesterol, HDL, LDL, glucose, insulin, insulin resistance, and β cell function evaluated by the homeostasis model assessment of insulin resistance (HOMA-IR) and β cell function (HOMA-β) at baseline and in response to the energy surplus. RESULTS Fasting serum PYY concentrations at baseline were not significantly different between the normal-weight, overweight, and obese subjects on the basis of dual-energy X-ray absorptiometry or BMI. Although the PYY concentration significantly increased due to overfeeding, no differences were observed between adiposity statuses. In addition, basal PYY was negatively correlated with the changes of total cholesterol, HDL, and LDL in normal weight. In addition, the increase in PYY after overfeeding was positively correlated with HDL cholesterol and glucose in normal-weight subjects. CONCLUSIONS Our findings suggest that fasting PYY concentrations are not associated with adiposity status. Moreover, the 7-d overfeeding challenge significantly increased fasting PYY, which is likely a protective response to the positive energy balance.

Association of RBP4 gene variants and serum HDL cholesterol levels in the Newfoundland population.

Retinol‐binding protein 4 (RBP4) is a novel adipokine that likely contributes to systemic insulin resistance and dyslipidemia. The role of genetic variations in RBP4 on phenotypes of glucose and lipid metabolism is not clear in humans. The purpose of this study was to examine five single‐nucleotide polymorphisms (SNPs) in the RBP4 gene to determine their relationship with markers of insulin resistance and serum lipids in the CODING Study. The CODING Study consists of 1,836 subjects recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMAIR), HOMA for β cell function (HOMAβ), total cholesterol (Chol), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and triglycerides were determined after a 12‐h fast. Five SNPs within RBP4 (rs3758539, G/A 5′ flanking region; rs61461737, A/G intron; rs10882280, C/A intron; rs11187545, A/G intron; and rs12265684, C/G intron) were genotyped using TaqMan validated or functionally tested SNP genotyping assays. After correcting for multiple testing, we observed a significant association between the minor allele of two noncoding SNPs (rs10882280 and rs11187545) and higher serum HDL‐C (P = 0.043 and 0.042, respectively). No significant associations were observed with any other parameter related to lipid metabolism. We also found no significant association between any variant sites and markers of insulin resistance. Our results suggest that genetic variations in RBP4 may play a role in the differences in serum HDL‐C levels in the NL population.

Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans

Background Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear. Objectives This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity. Methods LPA receptor mRNA levels were determined by qPCR in i) heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS)-fed male C57BL/6 mice, ii) 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii) human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients. Results LPA1-6 were expressed in myocardium and white adipose tissue from mice and humans, except for LPA3, which was undetectable in murine adipocytes and human adipose tissue. Obesity was associated with increased LPA4, LPA5 and/or LPA6 levels in mice ventricles and cardiomyocytes, HL-1 cells exposed to high palmitate, and human atrial tissue. LPA4 and LPA5 mRNA levels in human atrial tissue correlated with measures of obesity. LPA5 mRNA levels were increased in HFHS-fed mice and insulin resistant adipocytes, yet were reduced in adipose tissue from obese patients. LPA4, LPA5, and LPA6 mRNA levels in human adipose tissue were negatively associated with measures of obesity and cardiac surgery outcomes. This study suggests that obesity leads to marked changes in LPA receptor expression in the murine and human heart and white adipose tissue that may alter LPA receptor signaling during obesity.

No Association Between Visfatin ( NAMPT ) Gene Variants and Metabolic Traits in the Newfoundland Population

Objective Visfatin is a novel adipokine initially reported to exhibit insulin-mimetic effects that increase insulin sensitivity. Further studies indicate it may also be associated with obesity, serum lipids, and systemic inflammation. At the current time, the role of genetic variation in the visfatin gene (NAMPT) on these parameters is not clear. In the present study, we examined the association between 10 SNPs in NAMPT and insulin resistance, obesity, serum lipids and hsCRP levels. Research design and methods A total of 1838 subjects (413 men, 1425 women) were recruited from the ongoing CODING Study. All subjects were from the genetically homogenous population of Newfoundland and Labrador, Canada. BMI, waist circumference, waist-to-hip ratio, and body fat percentage (determined using DXA) were measured for all subjects. Serum glucose, insulin, HOMAIR, HOMAβ, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and hsCRP were also determined after a 12-hour fast. Ten SNPs in NAMPT were genotyped using TaqMan validated or functionally tested SNP genotyping assays including rs7789066 (A > G 5′ flanking region), rs3801266 (A > G intron), rs6963243 (G > C intron), rs2058539 (A > C intron), rs6947766 (C > T intron), rs4730153 (G > A intron), rs10808150 (G > A intron), rs2098291 (C > T intron), rs10953502 (T > C intron), and rs10953501 (A > G 3′ UTR). Results We observed no significant associations between any of the variants sites and any parameter of insulin resistance, body composition, serum lipids or hsCRP under an additive model with age and gender included as covariates. This was also true when both dominant and recessive models were applied. Conclusions Our results do not support a significant role for variations in NAMPT with differences in the measured variables in the Newfoundland population.