Gray matter volume increases induced by intragastric balloon treatment and their associations with neuroinflammation: A magnetic resonance study.

OBJECTIVE: We simultaneously performed structural MRI, 1H magnetic resonance spectroscopy, and whole-body hydration status assessment to evaluate brain changes in patients with morbid obesity treated with intra-gastric balloon (IGB) for six months. We asked, if changes in myo-inositol ratios (marker of neuroinflammation) are related to brain volume increases accompanying IGB-induced weight loss. METHODS: Twenty five patients with morbid obesity (OB, 43.9 ± 11.8 years, BMI = 49.1 ± 7.2, 12 females, 9 without co-morbid conditions) were treated with IGB for six months. They underwent magnetic resonance imaging at 3T one month before IGB insertion, three months after insertion (N = 19), and one month after IGB removal (N = 14). RESULTS: Insertion of IGB lead to 8.9% and 12.3% weight reduction over the first three months and over the entire treatment, respectively. Over the entire treatment, total gray matter volume increased by 2.0% (p = 0.009). These changes were mostly pronounced in the left precuneus and in the right frontal pole (>1.9%, p < 0.009). The increases in cortical volume in the right hemisphere and the left posterior cingulate cortical thickness over the entire treatment were significantly related to decreases in myo-inositol ratios measured over the first three months of the treatment (r < -0.740, p < 0.006). CONCLUSIONS: IGB treatment lead to brain structural improvements consistent with earlier studies of bariatric patients without co-morbid conditions. Our results also pointed to improvements in brain regions, where atrophy in other studies was related to type 2 diabetes and hypertension. The correlations point to neuroinflammation as one of the potential processes behind brain volume reductions in patients with morbid obesity.

Correction to: Real Life Changes in Physical Activity due to Intragastric Balloon Therapy and their Relationship to Improving Cognitive Functions: Preliminary Findings.

In the original article sections of the text include the term "(BLINDED)" rather than the correct text.

Real Life Changes in Physical Activity Due to Intragastric Balloon Therapy and Their Relationship to Improving Cognitive Functions: Preliminary Findings.

BACKGROUND: We evaluated if the intragastric balloon (IGB) treatment leads to the increase in physical activity (PA) and whether they are related to cognitive improvements. METHODS: Fourteen morbidly obese patients (151 ± 24 kg, BMI = 51.8 ± 6.5, 107 ± 26% excess weight, 43.3 ± 10.6 years) underwent 6-day-long, uninterrupted evaluations of PA 1 month before IGB insertion and 1 month after its removal. RESULTS: Active energy expenditure and physical activity duration increased by more than 80% (p < 0.001) whereas the number of steps per day by 20% (p = 0.016). There was a pattern of relationships between cognitive improvements and increases in PA (p < 0.05). In particular, working memory improvements correlated with the increase in time spent on light physical activities (r = 0.673, p = 0.004). CONCLUSION: The relationships suggest that an increase in physical activity mediates cognitive improvements in bariatric patients.

Changes in resting metabolic rate and body composition due to intragastric balloon therapy.

BACKGROUND: Intragastric balloon (IGB) insertion leads to dietary restriction; however, its neurohormonal actions were also described. Resting metabolic rate (RMR) adjusted for body mass (RMR/mass) seems to increase after bariatric interventions, whereas it generally decreases after caloric restriction-based therapies. However, no studies have evaluated the changes in body composition and RMR over IGB treatment. OBJECTIVE: To evaluate the relationships between changes in body composition, RMR, RMR/mass, and RMR adjusted for fat-free mass (FFM) (RMR/FFM) over IGB treatment lasting 6 months. SETTING: Single-center observational study. METHODS: Twenty-one morbidly obese patients treated with IGB (143 ± 20 kg, body mass index [BMI] = 49.5 ± 7.3, 98% ± 29% percent excess weight, 43.6 ± 12.6 yr) were enrolled. Changes in body composition, RMR, RMR/mass, and RMR/FFM were evaluated between 1 month before IGB insertion (time point 1 [TP1]) and 3 months thereafter (TP2). Fourteen patients were also assessed 1 month after IGB removal (TP3). RESULTS: There was a 9.5% reduction in weight, a 9.4% reduction in BMI, and 19.1% decrease in percent excess weight at TP2 (n = 21; P < .001); a further 6.5% reduction in weight and BMI and a 13.1% drop in percent excess weight (n = 14, P < .001) at TP3. They were accompanied by a 5.4% reduction in FFM between TP1 and TP2 (n = 21, P < .001). Compared with pretreatment values, at TP2 RMR was 12.5% lower (P < .001) but did not change thereafter. RMR/mass increased 12.4% between TP2 and TP3 (n = 14, P = .02) but on average did not change between TP1 and TP3. The results in the smaller cohort (n = 14) between TP1 and TP2 were consistent with results obtained for the entire cohort. Similar findings were obtained for RMR/FFM. The larger increases in RMR/mass between TP1 and TP3 were associated with more weight loss, larger drop in BMI, and more loss of excess weight (r < -.55, P < .03). CONCLUSION: This is the first study to evaluate the relationship between changes in body composition and RMR over IGB treatment. IGB therapy leads to both fat and fat-free mass reductions and RMR decreases. More weight reduction is associated with larger increases in RMR/mass.

Intragastric balloon therapy leads to normalization of brain magnetic resonance spectroscopic markers of diabetes in morbidly obese patients.

Elevated brain myo-inositol (m-Ins) concentration (a putative marker of neuroinflammation) has been reported in patients suffering from type 2 diabetes mellitus (T2DM). Obesity alone and T2DM have been found to be associated with a lower concentration of N-acetyloaspartate and N-acetylaspartylglutamate (tNAA, a marker of neuronal integrity, reflecting neuronal loss or metabolic derangement). It is not clear if these changes reverse with weight loss. The intra-gastric balloon (IGB) is an endoscopic bariatric therapy that leads to massive weight loss and improvement of glycemic control. In this study we evaluated if tNAA/tCr and m-Ins/tCr metabolite ratios are affected by weight loss, where tCr is the signal of creatine containing compounds. Twenty-three morbidly obese patients, 12 of them with T2DM (OD) and 11 without T2DM (OB), as well as 11 healthy controls of normal weight (CON), underwent single voxel spectroscopy at 3 T. Spectra were obtained within a region in the left parietal white matter one month before IGB insertion, three months after IGB insertion, and one month after IGB removal. Before IGB insertion, m-Ins/tCr was 15% higher in OD than in OB (p = 0.005) and 12% higher in OD than in CON (p = 0.03). m-Ins/tCr decreased significantly by 8% over the first three months after IGB insertion (p = 0.01) and remained normal after IGB removal. tNAA/tCr was normal in all groups throughout the study, pointing to normal brain metabolism. Normalization of m-Ins/tCr is consistent with remission of neuroinflammation in patients with T2DM. An evaluation of long-term effects of IGB treatment is necessary.

Long-Term Consumption of High-Fat Diet in Rats: Effects on Microglial and Astrocytic Morphology and Neuronal Nitric Oxide Synthase Expression.

Obesity in humans is associated with cognitive decline and elevated risk of neurodegenerative diseases of old age. Variations of high-fat diet are often used to model these effects in animal studies. However, we previously reported improvements in markers of memory and learning, as well as larger hippocampi and higher metabolite concentrations in Wistar rats fed high-fat, high-carbohydrate diet (HFCD, 60 % energy from fat, 28 % from carbohydrates) for 1 year; this diet leads to mild ketonemia (Setkowicz et al. in PLoS One 10:e0139987, 2015). In the present study, we follow up on this cohort to assess glial morphology and expression of markers related to gliosis. Twenty-five male Wistar rats were kept on HFCD and twenty-five on normal chow. At 12 months of age, the animals were sacrificed and processed for immunohistochemical staining for astrocytic (glial fibrillary acidic protein), microglial (Iba1), and neuronal (neuronal nitric oxide synthetase, nNOS) markers in the hippocampus. We have found changes in immunopositive area fraction and cellular complexity, as studied by a simplified Sholl procedure. To our knowledge, this study is the first to apply this methodology to the study of glial cells in HFCD animals. GFAP and Iba1 immunoreactive area fraction in the hippocampi of HFCD-fed rats were decreased, while the mean number of intersections (an indirect measure of cell complexity) was decreased in GFAP-positive astrocytes, but not in Iba1-expressing microglia. At the same time, nNOS expression was lowered after HFCD in both the cortex and the hippocampus.

Hypoxia and Coriolis Illusion in Pilots During Simulated Flight.

INTRODUCTION: Pilots' vision and flight performance may be impeded by spatial disorientation and high altitude hypoxia. The Coriolis illusion affects both orientation and vision. However, the combined effect of simultaneous Coriolis illusion and hypoxia on saccadic eye movement has not been evaluated. METHOD: A simulated flight was performed by 14 experienced pilots under 3 conditions: once under normal oxygen partial pressure and twice under reduced oxygen partial pressures, reflecting conditions at 5000 m and 6000 m (16,404 and 19,685 ft), respectively. Eye movements were evaluated with a saccadometer. RESULTS: At normal oxygen pressure, Coriolis illusion resulted in 55% and 31% increases in mean saccade amplitude and duration, respectively, but a 32% increase in mean saccade frequency was only noted for saccades smaller than the angular distance between cockpit instruments, suggesting an increase in the number of correction saccades. At lower oxygen pressures a pronounced increase in the standard deviation of all measures was noticed; however, the pattern of changes remained unchanged. DISCUSSION: Simple measures of saccadic movement are not affected by short-term hypoxia, most likely due to compensatory mechanisms.

Does Long-Term High Fat Diet Always Lead to Smaller Hippocampi Volumes, Metabolite Concentrations, and Worse Learning and Memory? A Magnetic Resonance and Behavioral Study in Wistar Rats.

BACKGROUND: Obesity is a worldwide epidemic with more than 600 million affected individuals. Human studies have demonstrated some alterations in brains of otherwise healthy obese individuals and elevated risk of neurodegenerative disease of old age; these studies have also pointed to slightly diminished memory and executive functions among healthy obese individuals. Similar findings were obtained in animal models of obesity induced by high fat diet. On the other hand, low carbohydrate high fat diets are currently promoted for losing weight (e.g., Atkin's style diets). However, the long-term effects of such diets are not known. Additionally, high fat diets leading to (mild) ketonemia were shown to improve brain function in elderly humans and in some animal models. AIM: To evaluate the hypothesis that long-term use of a high fat diet was associated with decreases in spatial memory, smaller hippocampi and hippocampi metabolite concentrations in Wistar rats. METHODS: Twenty five male Wistar rats were put on high fat diet (HFD; 60% calories from fat, 30% from carbohydrates) on their 55th day of life, while 25 control male rats (CONs) remained on chow. Adequate levels of essential nutrients were provided. Both groups underwent memory tests in 8-arm radial maze at 3rd, 6th, 9th, and 12th month. 1H magnetic resonance spectroscopy was employed to measure concentrations of tNAA (marker of neuronal integrity) at one month and one year, whereas MRI was used to evaluate hippocampal volumes. RESULTS: Obese rats (OBRs) consumed similar amount of calories as CONs, but less proteins. However, their protein intake was within recommended amounts. Throughout the experiment OBRs had statistically higher concentrations of blood ketone bodies than CONs, but still within normal values. At post-mortem assessment, OBRs had 38% larger fat deposits than CONs (p<0.05), as evaluated by volume of epididymis fat, an acknowledged marker of fat deposits in rats. Contrary to our expectations, OBRs had better scores of memory behavioral tasks than CONs throughout the experiment. At one year, their hippocampi were by 2.6% larger than in CONs (p = 0.05), whereas concentration of tNAA was 9.8% higher (p = 0.014). CONCLUSION: Long-term HFD in our study resulted in better memory, larger hippocampal volumes, as well as higher hippocampal metabolite concentrations, possibly due to increased levels of blood ketone bodies. The results should be interpreted with caution, as results from animal models do not necessarily directly translate in human condition.