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Background: Metabolic abnormalities are more associated with central obesity than peripheral obesity, but the underlying mechanisms are largely unknown. The present study was to identify serum metabolic biomarkers which distinguish metabolically unhealthy centrally obese (MUCO) from metabolically healthy peripherally obese (MHPO) individuals. Methods: A two-stage case-control study design was employed. In the discovery stage, 20 individuals (10 MHPO and 10 MUCO) were included and in the following validation stage, 79 individuals (20 normal weight (NW), 30 MHPO, 29 MUCO) were utilized. Study groups were matched for age, sex, physical activity and total dietary calorie intake with MHPO and MUCO additionally matched for BMI. Metabolic abnormality was defined as: 1) HOMA-IR>4.27 (90th percentile), 2) high-density lipoprotein cholesterol < 1.03 mmol/L in men and < 1.30 mmol/L in women, 3) fasting blood glucose ≥ 5.6 mmol/L, and 4) waist circumference > 102 cm in men and > 88 cm in women. MUCO individuals had all of these abnormalities whereas MHPO and NW individuals had none of them. A targeted metabolomics approach was performed on fasting serum samples, which can simultaneously identify and quantify 186 metabolites. Results: In the discovery stage, serum leucine, isoleucine, tyrosine, valine, phenylalanine, alpha-aminoadipic acid, methioninesulfoxide and propionylcarnitine were found to be significantly higher in MUCO, compared with MHPO group after multiple testing adjustment. Significant changes of five metabolites (leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine) were confirmed in the validation stage. Conclusions: Significantly higher levels of serum leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine are characteristic of metabolically unhealthy centrally obese patients. The finding provides novel insights into the pathogenesis of metabolic abnormalities in obesity. [ABSTRACT FROM AUTHOR]

Background: Ghrelin and peptide YY (PYY) are appetite regulating hormones secreted from the gastrointestinal tract (gut). Aside from their known effect on energy homeostasis, accumulating data indicates that these gut hormones also affect bone metabolism. However, data regarding the influence of ghrelin and PYY on bone density in humans is very limited, and the results are inconclusive. Therefore, this study was designed to investigate the potential association between circulating ghrelin and PYY with bone density indices in the general population. Methods: A total of 2257 adult subjects from the CODING (Complex Diseases in the Newfoundland Population: Environment and Genetics) study participated in this investigation. Acylated ghrelin and total PYY were measured in serum after a 12-hour fasting, with the Enzyme-Linked Immunosorbent Assay (ELISA) method. Bone mineral density was measured by dual-energy X-ray absorptiometry at the spine, femoral neck, and total hip. Multiple regression analyses adjusting for age, BMI, physical activity, smoking, and alcohol consumption were employed to analyze the association between serum ghrelin and PYY with bone mineral density parameters. Results: Significant positive associations of ghrelin concentration with L2-L4 BMD, L2-L4 Z-score, femoral neck BMD, femoral neck Z-score, total hip BMD, and total hip Z-score were found in women. No significant correlations between ghrelin and bone density indices were present in men. After dividing the female group into premenopausal and post-menopausal, ghrelin was positively correlated with femoral neck Z-score, and total hip Z-score in pre-menopausal women and L2-L4 BMD, and Z-score in post-menopausal group. Moreover, no significant association was discovered between serum PYY and bone density at any site. Conclusion: Our results suggest a beneficial association of circulating ghrelin concentration with bone density in women at the population level. This association is independent of major confounding factors including BMI, physical activity, age, alcohol consumption, and smoking. Effect of menopause on this association seemed to be site specific. However, PYY does not seem to be associated with bone density parameters. [ABSTRACT FROM AUTHOR]

Background: Glucagon-like Peptide-1 (GLP-1) is an incretin hormone secreted from the gastrointestinal tract that facilitates the glucose-dependent insulin response. Additionally, GLP-1 is thought to be involved in energy homeostasis. Currently little is known about GLP-1's responsiveness to an energy surplus, a fundamental cause of obesity and diabetes. Our objective was to examine the response of serum GLP-1 to short-term (7 day) overfeeding in young men. Methods: Seventy-two young men from the Canadian province of Newfoundland were recruited for the study. For 7-days, the subjects consumed 70% more calories than required at baseline. Various measurements including: anthropometrics, body composition, markers of glucose/lipid metabolism and serum total GLP-1, were taken at a fasted state before (day 1) and after (day 8) the challenge. Paired t-test analyses were used to assess the change in variables after the overfeeding period. Additionally, the relationship between serum GLP-1 and the measured variables at baseline and change due to overfeeding were analyzed. Results: Serum GLP-1 was significantly increased in all groups in response to the 7-day energy surplus, indicating the increase was independent of adiposity status. There was no significant difference in fasting GLP-1 at baseline between the normal weight and overweight/obese groups. At baseline, GLP-1 concentration negatively correlated with HDL-cholesterol and positively correlated with triacylglycerols and markers of insulin resistance in the overweight/obese group. Also GLP-1 was negatively correlated with change in percent gynoid fat in the overweight/obese subjects. Percent change in GLP-1 was negatively associated with percent change in gynoid fat in the normal weight group and positively associated with percent change in cholesterol in the overweight/obese group. Percentage change of circulating triacylglycerols was positively associated with percent change in GLP-1 in both adiposity groups. Conclusion: Our findings showed that GLP-1 serum concentration is not a significant factor in determining obesity status. The increase of GLP-1 in all subjects regardless of obesity status, suggest GLP-1 serves as a protective role, counteracting energy surplus. [ABSTRACT FROM AUTHOR]

Background: Metabolic abnormalities are more associated with central obesity than peripheral obesity, but the underlying mechanisms are largely unknown. The present study was to identify serum metabolic biomarkers which distinguish metabolically unhealthy centrally obese (MUCO) from metabolically healthy peripherally obese (MHPO) individuals., Methods: A two-stage case-control study design was employed. In the discovery stage, 20 individuals (10 MHPO and 10 MUCO) were included and in the following validation stage, 79 individuals (20 normal weight (NW), 30 MHPO, 29 MUCO) were utilized. Study groups were matched for age, sex, physical activity and total dietary calorie intake with MHPO and MUCO additionally matched for BMI. Metabolic abnormality was defined as: 1) HOMA-IR > 4.27 (90(th) percentile), 2) high-density lipoprotein cholesterol < 1.03 mmol/L in men and < 1.30 mmol/L in women, 3) fasting blood glucose ≥ 5.6 mmol/L, and 4) waist circumference > 102 cm in men and > 88 cm in women. MUCO individuals had all of these abnormalities whereas MHPO and NW individuals had none of them. A targeted metabolomics approach was performed on fasting serum samples, which can simultaneously identify and quantify 186 metabolites., Results: In the discovery stage, serum leucine, isoleucine, tyrosine, valine, phenylalanine, alpha-aminoadipic acid, methioninesulfoxide and propionylcarnitine were found to be significantly higher in MUCO, compared with MHPO group after multiple testing adjustment. Significant changes of five metabolites (leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine) were confirmed in the validation stage., Conclusions: Significantly higher levels of serum leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine are characteristic of metabolically unhealthy centrally obese patients. The finding provides novel insights into the pathogenesis of metabolic abnormalities in obesity.