Hypothalamic Gliosis by MRI and Visceral Fat Mass Negatively Correlate with Plasma Testosterone Concentrations in Healthy Men.

OBJECTIVE: This study aimed to determine whether a relationship was evident between gliosis in the mediobasal hypothalamus (MBH) and plasma testosterone concentrations in men. METHODS: A total of 41 adult men (aged 18-50 years) from 23 twin pairs underwent fasting morning blood draw and brain magnetic resonance imaging. T2 relaxation time was used to quantify gliosis in the MBH and control areas in the putamen and amygdala. Plasma concentrations of testosterone and 17ß-estradiol were measured by liquid chromatography-tandem mass spectrometry. Body composition including visceral adiposity was measured by dual x-ray absorptiometry. RESULTS: A negative association was found between MBH T2 relaxation time and plasma concentrations of both free and total testosterone (r = -0.29, P < 0.05 and r = -0.37, P < 0.01, respectively). Visceral adiposity exhibited a negative correlation with plasma total testosterone concentration (r = -0.45, P = 0.001) but a positive correlation with MBH T2 relaxation time (r = 0.24, P = 0.03). The negative correlation between plasma total testosterone and MBH T2 relaxation time remained significant after adjustment for visceral adiposity, age, BMI, and insulin resistance. CONCLUSIONS: In healthy men across a range of BMIs, MBH gliosis was associated with higher visceral adiposity but lower endogenous testosterone. These findings suggest that MBH gliosis could provide novel mechanistic insights into gonadal dysfunction in men with obesity.

Associations of adipose and muscle tissue parameters at colorectal cancer diagnosis with long-term health-related quality of life.

PURPOSE: Increased visceral adiposity (visceral obesity) and muscle wasting (sarcopenia) at colorectal cancer (CRC) diagnosis, quantified by computed tomography (CT) image analysis, have been unfavorably associated with short-term clinical outcomes and survival, but associations with long-term health-related quality of life (HRQoL) have not been investigated. We studied associations of visceral adiposity, muscle fat infiltration, muscle mass, and sarcopenia at CRC diagnosis with HRQoL 2-10 years post-diagnosis. METHODS: A cross-sectional study was conducted in 104 stage I‒III CRC survivors, diagnosed at Maastricht University Medical Center+, the Netherlands (2002-2010). Diagnostic CT images at the level of the third lumbar vertebra were analyzed to retrospectively determine visceral adipose tissue area (cm2); intermuscular adipose tissue area (cm2) and mean muscle attenuation (Hounsfield units) as measures of muscle fat infiltration; and skeletal muscle index (SMI, cm2/m2) as measure of muscle mass and for determining sarcopenia. RESULTS: Participants showed a large variation in body composition parameters at CRC diagnosis with a mean visceral adipose tissue area of 136.1 cm2 (standard deviation: 93.4) and SMI of 47.8 cm2/m2 (7.2); 47% was classified as being viscerally obese, and 32% as sarcopenic. In multivariable linear regression models, associations of the body composition parameters with long-term global quality of life, physical, role and social functioning, disability, fatigue, and distress were not significant, and observed mean differences were below predefined minimal important differences. CONCLUSIONS: Although visceral obesity and sarcopenia are relatively common at CRC diagnosis, we found no significant associations of these parameters with long-term HRQoL in stage I-III CRC survivors.

Childhood maltreatment increases the risk for visceral obesity.

OBJECTIVE: The reports regarding the associations between childhood maltreatment (CM) and body fat composition remain heterogeneous in humans although they are indicated in preclinical studies. In addition, the effects of CM subtypes on different types of body fat are unclear. Thus, in this study, the associations between CM and its subtypes with body fat were determined and the potential pathways were explored. METHODS: The participants were assessed for a history of CM by the Childhood Trauma Questionnaire and were divided into the CM group (with CM exposures) and non-CM group (without CM exposures). Body composition was measured by dual-energy X-ray absorptiometry. Salivary and blood samples were provided by the subjects. RESULTS: Compared with the non-CM group, subjects with a history of CM had greater visceral fat mass (1,136 ± 160 vs. 836 ± 116 g, P < 0.05) but not total body fat, android fat, body mass index, or waist-to-hip ratio. In addition, subjects with CM had a blunted cortisol awakening response and elevated inflammatory factors. Correlation analysis indicated that CM subtypes had differential effects on visceral adiposity and cortisol awakening response. CONCLUSIONS: It is suggested by our results that CM exposure is linked with increased visceral fat deposition, and the perturbation of the hypothalamic-pituitary-adrenal axis activity and activation of the immune system may be two potential pathways through which this relationship is explained.

Peripheral and visceral fat changes following a treatment switch to a non-thymidine analogue or a nucleoside-sparing regimen in HIV-infected subjects with peripheral lipoatrophy: results of ACTG A5110.

BACKGROUND: Switching a thymidine analogue to a non-thymidine analogue or changing to a nucleoside-sparing regimen has been shown to partially reverse peripheral lipoatrophy. The current study evaluated both approaches. METHODS: Subjects at 15 AIDS Clinical Trial Group sites receiving thymidine analogue stavudine- or zidovudine-containing regimens with plasma HIV RNA < or =500 copies/mL and lipoatrophy were prospectively randomized to: (i) switch the thymidine analogue to abacavir; (ii) discontinue all antiretrovirals and switch to lopinavir/ritonavir plus nevirapine (LPV/r+NVP); or (iii) delay switching for 24 weeks (ClinicalTrials.gov identifier: NCT00028314). Single-slice computer tomography of mid-thigh and abdominal fat and metabolic and virological/immunological parameters were measured at baseline and weeks 24 and 48. RESULTS: Among the 101 patients enrolled, there were significant subcutaneous thigh fat and subcutaneous abdominal tissue (SAT) increases over time and decreases in visceral adipose tissue to total adipose tissue (VAT:TAT) ratios for both interventions, and a decrease in VAT for abacavir. CD4 increased in the LPV/r+NVP arm. LPV/r+NVP had a significantly shorter time to grade 3 or higher toxicity (P = 0.007), but discontinuation rates were similar. Glucose levels did not change, but insulin decreased in the LPV/r+NVP arm. Lipids tended to increase in the LPV/r+NVP arm. CONCLUSIONS: Switching stavudine or zidovudine to a non-thymidine analogue or changing to a nucleoside reverse transcriptase inhibitor-sparing regimen is associated with qualitatively similar improvements in thigh fat, SAT and VAT:TAT ratio at 48 weeks. Abacavir also resulted in VAT reductions and LPV/r+NVP resulted in CD4 count increases.

Relation of body composition to body mass index in HIV-infected patients with metabolic abnormalities.

OBJECTIVE: To determine visceral adiposity (VAT), subcutaneous adiposity (SAT), and regional body adipose differences between HIV-infected and non-HIV-infected subjects in relation to body mass index (BMI) and World Health Organization BMI categories. DESIGN, SETTING, AND PARTICIPANTS: Analyses were conducted of 306 HIV-infected and 107 community-derived HIV-negative subjects evaluated for metabolic studies between 1999 and 2006. Analyses were stratified by gender. Additional analyses were performed stratifying subjects by metabolic syndrome status. RESULTS: HIV-infected men and women demonstrated decreased total extremity fat by 1.1 kg and 0.85 kg, respectively, relative to non-HIV-infected control subjects. VAT was increased among HIV-infected men and women in the normal (18.5 to 24.9 kg/m2) and overweight (25.0 to 29.9 kg/m2) categories relative to control subjects but not among those in the obese category (> or =30.0 kg/m2). In contrast, abdominal SAT was reduced among HIV-infected men in the normal and overweight categories but was similar among HIV-infected women and control subjects in these categories. Abdominal SAT was increased among HIV-infected women in the obese category relative to control subjects. Similar results were obtained limiting the analysis to HIV-infected (n = 204) and control subjects (n = 89) without the metabolic syndrome. CONCLUSIONS: Peripheral lipoatrophy is a consistent finding among HIV-infected men and women with metabolic abnormalities. Relative increases in VAT are most pronounced among male and female HIV-infected subjects in the normal weight and overweight categories. Gender differences in abdominal SAT accumulation are observed, with preservation of SAT among HIV-infected women relative to control subjects.