P. Babu Balagopal

Decreased circulating levels of spexin in obese children

CONTEXT Spexin is a novel peptide that is implicated in obesity and related energy homeostasis in animals and adult humans. Little is known about its role in children. OBJECTIVE The aim of the current study was to determine the potential role of Spexin in obese children and explore its relationships with various cardiometabolic risk factors. DESIGN AND PARTICIPANTS This was a cross-sectional study composed of 69 children (51 obese and 18 normal weight; age 15.3 ± 0.26 y). OUTCOME MEASURES Spexin was measured using a specific enzyme-linked immunosorbent assay. Leptin, total and high-molecular-weight adiponectin, IL-6, high-sensitivity C-reactive protein, glucose, and insulin were also measured. Mann-Whitney U test, Pearson and Spearman rank correlations, logistic regression, and cluster analysis were used for the analysis and interpretation of the data. RESULTS Spexin levels were significantly lower in obese vs normal-weight children, median(IQR) (0.33 ng/mL [0.27-0.44] vs 0.42 ng/mL [0.33-0.55]; P = .024), but did not correlate with other adipokines and/or insulin and glucose levels. Ordinal categorical variables of Spexin showed a strictly reverse association of obesity with the level of Spexin. Cluster analysis of Spexin and body mass index z score resulted in splitting the participants into normal-weight and obese-weight groups with high accuracy. CONCLUSIONS Lower circulating levels of Spexin in obese children compared with their normal-weight counterparts and the ability to discriminate obese and normal-weight groups based on Spexin concentration enabled us to suggest a potential role for this novel peptide in childhood obesity. The clinical significance of these findings needs additional investigation.

Pre-heparin lipoprotein lipase mass as a potential mediator in the association between adiponectin and HDL-cholesterol in type 2 diabetes

Highlights • We examined pre-heparin LPL mass in type 2 diabetes mellitus (T2DM).• Association of adiponectin, pre-heparin LPL mass, and HDL-C was examined in T2DM.• Pre-heparin LPL mass may mediate the adiponectin and HDL-C association in T2DM.

Physical activity levels and hepatic steatosis: a longitudinal follow up study in adults

This study aimed to evaluate the impact of physical activity (PA) on the course of hepatic steatosis (HS) in adults.

Roux-en-Y gastric bypass surgery in youth with severe obesity: 1-year longitudinal changes in spexin

BACKGROUND Spexin is a novel peptide predominantly produced in human white adipose tissue and has recently been implicated as a potential signal in the regulation of body weight, energy homeostasis, and satiety. The effect of bariatric surgery on spexin is unknown. OBJECTIVES To study the effect of Roux-en-Y gastric bypass (RYGB) surgery on endogenous spexin concentration and various risk factors of type 2 diabetes and cardiovascular disease in youth with severe obesity. SETTING University hospital, United States METHODS: Spexin, body mass index (BMI), insulin, glucose, total and high molecular weight adiponectin, leptin, and high sensitivity C- reactive protein were measured longitudinally (baseline, 6 mo, and 12 mo) after RYGB surgery in girls with severe obesity (n = 12; age = 16.7 ± 1.5 years; BMI = 51.6 ± 2.9 kg/m2). RESULTS Serum spexin concentration increased (P = .01) at 6 months after surgery and stabilized afterward. Spexin level correlated negatively with homeostatic model assessment insulin resistance, HOMA-IR (Spearman correlation r = -.796, P < .001) and positively with high molecular weight adiponectin (Spearman correlation r = .691, P = .011). The change in spexin concentration, from baseline to 6 months after surgery, was inversely correlated with the corresponding change in BMI (Spearman correlation r = -.573, P = .051). Furthermore, the 6-month changes in spexin and HOMA-IR were inversely correlated (slope [standard error, SE] = -.0084 (.0019), P = .001)], even after adjusting for the change in BMI. CONCLUSIONS The enhancement of circulating spexin concentration in response to RYGB and correlations with beneficial postoperative changes in various adipokines in youth are novel findings that require further validation.

Vitamin D Status and Cardiovascular Risk in Obesity: Effect of Physical Activity in Nonvitamin D Supplemented Adolescents

BACKGROUND The relationship among inadequate vitamin D status, obesity, and cardiometabolic risk and the potential impact of physical activity-based interventions on vitamin D status are poorly characterized in children. This study aimed to address these issues. METHODS We studied a total of 21 adolescents (15 obese and 6 normal weight; age: 14-18 years; Tanner stage>IV). Adolescents with obesity (n = 15) underwent a randomized controlled (8 in the intervention group and 7 in the control group) 3-month physical activity-based lifestyle intervention. 25-Hydroxy vitamin D [25(OH)D] by mass spectrometry, adiponectin, leptin, high-sensitivity C-reactive protein (CRP), insulin, and glucose were measured and body composition was assessed by dual-energy x-ray absorptiometry (DXA). Analysis of covariance and mixed-effects model were used to compare mean change in 25(OH)D between intervention and nonintervention groups. Bootstrap method was used to validate the estimates and principle component analysis reduced the variables in the data for adjustment. RESULTS 25(OH)D was lower (P < 0.001) in the obese versus lean adolescents. Homeostasis model assessment-insulin resistance, CRP, fat mass (FM), and body mass index z-score were negatively correlated with baseline 25(OH)D, while adiponectin showed a positive correlation. After adjustment for baseline biomarkers of cardiometabolic risk, the concentration of 25(OH)D increased in the obese intervention group (P = 0.06), but not in the nonintervention group. Fat-free mass increased and FM decreased (P < 0.05 for both) in the intervention group. The magnitudes of increase in 25(OH)D and decrease in FM directly correlated (P < 0.05). CONCLUSIONS The increase in circulating 25(OH)D concentration by physical activity-based lifestyle-only intervention in adolescents with obesity, who did not receive vitamin D supplementation, suggests a putative independent role of physical activity-based interventions in the regulation of vitamin D status and potentially in the mitigation of risk factors of cardiovascular disease.

Effect of parathyroidectomy on osteopontin and undercarboxylated osteocalcin in patients with primary hyperparathyroidism

ABSTRACT Purpose: Surgical treatment for primary hyperparathyroidism (PHPT) improves bone metabolism. Osteocalcin (OC) and its undercarboxylated form (ucOC) are associated with bone and energy metabolism. Osteopontin (OPN), a multifunctional protein expressed in bone, is involved in resorption, along with β-carboxyl-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and osteoprotegerin (OPG). Our aim was to investigate these biomarkers of bone metabolism in patients with PHPT. Methods: We examined 30 individuals with PHPT, in a clinical research facility, before and 1 month following parathyroidectomy. Circulating levels of OC, ucOC, OPN, β-CTX, and OPG were examined as bone biomarkers along with inflammatory markers (e.g., interleukin-6 [IL-6], lipocalin-2), insulin resistance (i.e., homeostasis model assessment for insulin resistance [HOMA-IR]), adiposity (i.e., leptin, adiponectin), PTH, calcium, 25-hydroxyvitamin D, creatinine, and demographics. Results: Participants (27 females/3 males) were 60 ± 9 (mean±SD) years old. There was a significant reduction of ucOC (7.9 ± 5.1 [median±SIQR] vs. 6.6 ± 3.7 ng/mL, p = 0.022) and OPN (75.4 ± 14.5 vs. 54.5 ± 9.2 ng/mL, p < 0.001) pre- versus post-parathyroidectomy. There were no univariate differences postoperatively for IL-6, HOMA-IR, leptin, or adiponectin. Regression analysis showed that postoperative levels of adiponectin, IL-6, and OPN were significantly associated with ucOC, while adjusting for PTH and albumin corrected calcium levels (model R2 = 0.610, p = 0.001). With OPN as the dependent variable, higher adiponectin and lower ucOC were significantly associated with lower OPN levels postoperatively (model R2 = 0.505, p = 0.010). Conclusion: The lower 1-month postoperative OPN and ucOC levels in PHPT seem to indicate reduced bone resorption. Decreased ucOC levels may also suggest lower energy demands postoperatively.

Self-initiated physical activity is associated with high sensitivity C-reactive protein: A longitudinal study with 5,030 adults

BACKGROUND AND AIMS Structured regular exercise programs decrease high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation in adults. Longitudinal effects of self-initiated physical activity levels (PAL) on hsCRP are less clear. This study evaluated the association of longitudinal changes in hsCRP in relation to modifications in PAL, over time, in a large sample of adults. METHODS Participants included 5030 adults, 4045 (80%) males, undergoing routine health screening examinations. Elevated level of hsCRP was defined as ≥3 mg/L. Self-reported PAL, height, weight, blood pressure and blood samples were collected at baseline and after a median of 2.9 years (P25th 1.97 and P75th 4.37 yrs). Participants were stratified according to their PAL at baseline and follow-up as: i) persistently physically inactive; ii) became physically inactive; iii) became physically active; iv) persistently physically active (active both at baseline and follow-up). RESULTS Persistently physically active participants had lower odds of having higher hsCRP (OR = 0.35 [95% CI: 0.25 to 0.48]). The maintenance of high PAL was associated with lower hsCRP in both sexes (men: OR = 0.44 [0.30 to 0.65] and women: OR = 0.35 [0.16 to 0.76]). Participants with overweight/obesity (OR = 0.43 [95% CI: 0.29 to 0.63]) and smokers (OR = 0.123 [95% CI: 0.03 to 0.60]) who were persistently active had lower odds of having higher hsCRP compared to physically inactive peers. CONCLUSIONS Self-initiated PAL was longitudinally associated with hsCRP in adults. The data suggest that the initiation or maintenance of PA attenuates the low-grade inflammatory state, independent of sex, body weight and smoking status.