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

Abstract

Objective: To determine whether a relationship was evident between gliosis in the mediobasal hypothalamus (MBH) and plasma testosterone concentrations in men Methods: 41 adult men (ages 18–50 years) from 23 twin pairs underwent fasting morning blood draw and brain MRI. T2 relaxation time was used to quantify gliosis in the MBH and control areas in the putamen and amygdala. Plasma concentrations of testosterone and 17β-estradiol were measured by LC-MS/MS. 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.

Roux-en-Y gastric bypass surgery progressively alters radiologic measures of hypothalamic inflammation in obese patients

“…In the present study, we asked whether RYGB attenuates obesity-associated hypothalamic inflammation in humans using established radiologic techniques (28)(29)(30)(31)(32)(42)(43)(44)(45)(46). We also used a potentially novel, more sensitive analysis method that entails a straightforward division of T2W by T1W images to enhance waterbased contrast (39,40).…”

Initial evidence for hypothalamic gliosis in children with obesity by quantitative T2 MRI and implications for blood oxygen‐level dependent response to glucose ingestion

“…Moreover, the association of gliosis with adiposity was also suggested for visceral fat deposition. 28 Thus, hypothalamic gliosis may be linked to fat deposition with negative metabolic consequences. As such, the findings are informative regarding previous results in humans showing greater insulin resistance among adults with gliosis, independent of body fat mass.…”

Immunometabolic Changes in Glia – A Potential Role in the Pathophysiology of Obesity and Diabetes

“…Inflammation in the brain is a key feature of disease pathology seen in experimental models of obesity and diabetes ( De Souza et al, 2005 , Thaler et al, 2012 ). Evidence from human brain imaging studies also supports the existence of obesity-associated neuroinflammation in both adults and children ( Thaler et al, 2012 , Schur et al, 2015 , Berkseth et al, 2018 , Sewaybricker et al, 2019 ).…”

“…Markers of both microgliosis and astrogliosis have been observed within the hypothalamus of obese animals and humans ( Horvath et al, 2010 , García-Cáceres et al, 2011 , Fuente-Martín et al, 2012 , Thaler et al, 2012 , Buckman et al, 2013 , Berkseth et al, 2014 , Gao et al, 2014 , Schur et al, 2015 , Berkseth et al, 2018 ). Extra-hypothalamic changes have also been observed ( Pistell et al, 2010 , Buckman et al, 2013 ), with the hippocampus being the most studied brain region in this regard.…”