Inverse Association Between Hypothalamic N-Acetyl Aspartate/Creatine Ratio and Indices of Body Mass in Adolescents with Obesity.

BACKGROUND: Approximately 10% of adolescents worldwide are overweight or obese, hence the urgent and universal need to elucidate possible mechanisms that lead to obesity in the adolescent population. OBJECTIVES: We examined the hypothalamic metabolism and its relationship with physical development in obese and eutrophic adolescents. METHODS: We performed a case-control study with 115 adolescents between 11 and 18 years of age, to compare obese (BMI z-score ≥ 2) and nonobese individuals (eutrophic controls; BMI z-score ≤ 1). The following hypothalamic metabolite ratios were examined as primary outcomes: glutamate/creatine (Cr), the sum of glutamate and glutamine/Cr, N-acetylaspartate (NAA)/Cr, myoinositol/Cr, and total choline/Cr (glycerophosphocholine +  phosphocholine/Cr), quantified by magnetic resonance spectroscopy. BMI z-scores, pubertal status, and scores on the Yale Food Addiction Scale, the Binge Eating Scale, and the Child Depression Inventory were assessed as secondary outcomes. Pearson coefficients (r) or nonparametric Spearman correlation (rho) analyses were performed between hypothalamic metabolite ratios and other parameters, such as BMI z-scores, physical development, food habits, depression symptoms, and serum protein concentrations (cytokines, hormones, and neuropeptides). RESULTS: Adolescents with obesity showed a lower hypothalamic NAA/Cr ratio (0.70 ± 0.19) compared to their eutrophic counterparts (0.84 ± 0.20; P = 0.004). The NAA/Cr ratio was negatively correlated with BMI z-scores (r = -0.25; P = 0.03) and serum insulin (rho = -0.27; P = 0.04), C-peptide (rho = -0.26; P = 0.04), amylin (r = -0.27; P = 0.04), ghrelin (rho = -0.30; P = 0.02), and neuropeptide Y (r = -0.27; P = 0.04). Also, the NAA/Cr ratio was positively correlated with circulating IL-8 levels (rho = 0.26; P = 0.04). CONCLUSIONS: High BMI z-scores are associated with lower hypothalamic NAA/Cr ratios. The negative correlations found between the NAA/Cr ratio and serum cytokines, hormones, and neuropeptides suggest a broad cross-talk linking hormonal imbalances, neurohumoral alterations, and hypothalamic functions in adolescents with obesity.

Sex dimorphism in inflammatory response to obesity in childhood.

BACKGROUND: Childhood overweight and obesity are a global concern, with prevalence rising dramatically over the last decades. The condition is caused by an increase in energy intake and reduction of physical activity, leading to excessive fat accumulation, followed by systemic chronic inflammation and altered function of immune cell responses. This study aimed at providing new insights regarding sex-specificity on the inflammatory response to obesity in the young patient. DESIGN: Forty-three Brazilian obese adolescents (Female = 22 and Male=21, BMI (body mass index) Z-score average = 2.78 ± 0.51) and forty-nine eutrophic adolescents (Female = 24 and Male = 25, BMI Z-score average = -0.35 ± 0.88) were enrolled in the study. Anthropometrical analyses and blood cell counts were carried out. Using Luminex®xMAP™ technology, circulating serum cytokines, chemokines, and inflammatory biomarkers were analyzed. Two-way ANOVA test, Tukey's test, and Spearman's correlation coefficient were employed, with a significance threshold set at p < 0.05. RESULTS: We identified increased levels of serum amyloid A (SAA), platelets, and leukocytes solely in male obese patients. We found a noteworthy sex-dependent pattern in regard to inflammatory response: obese boys showed higher TNFß, IL15, and IL2 and lower IL10 and IL13, while obese girls showed increased TNFα, CCL3, CCL4, and IP10 content in the circulation. BMI Z-score was significantly linearly correlated with neutrophils, leukocytes, platelets, SAA, TNFα, CCL3, CCL4, IP10, and IL13 levels within the entire cohort (non-sex-dependent). CONCLUSIONS: Our data support a complex relationship between adiposity, blood cell count, and circulating inflammatory cytokine content. High SAA levels suggest that this factor may play a critical role in local and systemic inflammation. In the eutrophic group, females presented a lower status of inflammation, as compared to males. Both obese boys and girls showed an increased inflammatory response in relation to eutrophic counterparts. Taken together, results point out to clear sex dimorphism in the inflammatory profile of obese adolescents.

Costs associated with depression and obesity among cardiovascular patients: medical expenditure panel survey analysis.

BACKGROUND: There is a lack of information on the cost of depression associated with metabolic syndrome and cardiovascular diseases in the literature. METHODS: We evaluated the synergistic effects of depression and obesity on total expenditures for cardiovascular conditions using data from the Medical Expenditure Panel Survey (MEPS) database. We analyzed MEPS data from 1996 to 2017 comprising adult cardiovascular subjects. We categorized individuals following a combination of International Classification of Diseases ICD-9-CM and ICD-10 codes, and depression symptoms as evaluated using the Patient Health Questionnaire-2 (PHQ-2) depression screening tool. Our sample comprised cardiovascular patients aged 18 years and older, with a body mass index (BMI) between 18.5 and 60. Our study comprised unweighted sample of 96,697 (weighted sample of 938,835,031) adults, a US-nationwide representative sample of cardiovascular disease patients. The four response categories were: no depression; unrecognized depression; asymptomatic depression; and symptomatic depression. Our evaluated outcomes were total annual healthcare expenditures, including dental, emergency room, hospital outpatient, hospital inpatient, office-based, prescription, and home health care expenses. RESULTS: Asymptomatic and symptomatic depression was more frequent among obese individuals than in individuals with a normal BMI (p <  0.001). Total expenditure was highest among symptomatic depression individuals (17,536) and obese (9871) with cardiovascular disease. All the expenditure outcomes were significantly higher among symptomatic depression individuals than those without depression (p <  0.001), except for dental costs. All healthcare expenditures associated with obesity were higher compared to individuals with normal BMI with p <  0.001, except for emergency and home healthcare costs. Most importantly, among obese individuals, all healthcare expenditures were significantly higher (p <  0.001) in those with symptomatic depression than those without depression, except for dental costs, where the difference was not significant (0.899). Therefore, obesity and depression entail increased expenses in patients with cardiovascular disease. CONCLUSIONS: We found incremental expenditures among unrecognized, asymptomatic, and symptomatic depressed individuals with obesity compared to non-depressed, non-obese subjects. However, these are preliminary results that should be further validated using different methodologies.

Sex-Dependent Dyslipidemia and Neuro-Humoral Alterations Leading to Further Cardiovascular Risk in Juvenile Obesity.

Objective: Childhood obesity is a growing concern as the World Health Organization (WHO) states that ~10% of adolescents worldwide are overweight or obese. This condition is the reflex of energy imbalance between the calories consumed and those expended. Sex-related responses associated with dyslipidemia, hormonal alterations, and neuro-humoral disruptions in childhood obesity are the focus of the present investigation. Methods: Ninety-two Brazilian adolescents were enrolled and divided between obese and eutrophic groups. Obesity was assessed using body mass index Z-score according to age and weight. Anthropometrical analyses, blood pressure, blood lipids, metabolism-regulating hormones, and neuropeptides were carried out. Results: Systolic blood pressure was higher in female and male patients with obesity. Obese females presented alterations in lipid profile and an augment of cardiovascular disease prediction ratios TC/HDL, TG/HDL, LDL/HDL, and VLDL/HDL. The levels of leptin, GIP, and neuropeptide showed sex-dimorphism in obesity. The obese adolescents presented increased levels of circulating insulin, c-peptide, amylin, glucagon, and GLP-1. Correlation analysis showed significant linearity between body mass index, blood pressure, lipids, lipoproteins, hormones, and neuropeptides content. Conclusions: Our data support an existing link associating hypertension, dyslipidemia, and neuro-hormonal imbalance in childhood obesity. We also described a sex-dependent pattern in childhood obesity-associated dyslipidemia and blood pressure in female patients with obesity solely.