Increased orexin A concentrations in cerebrospinal fluid of patients with behavioural variant frontotemporal dementia

Orexins are hypothalamic neuropeptides that regulate several physiological functions, such as appetite, arousal, cognition, stress, sleep and metabolism. Emerging pieces of evidence suggest an orexinergic dysfunction in several neuropsychiatric disorders, including depression, anxiety and addiction. A syndromic overlap between behavioural variant frontotemporal dementia (bvFTD) and several psychiatric disorders was recently demonstrated. Therefore, we analysed cerebrospinal fluid (CSF) orexin A concentrations of 40 bvFTD and 32 non-demented patients, correlating neuropeptide concentrations with several clinical characteristics. A significant increase of orexin A concentrations was found in bvFTD patients when compared to controls (p<0.001). CSF orexin A concentration showed a correlation with Mini-Mental State Examination scores, drug assumption, history of compulsive behaviour and extrapyramidal signs. Moreover, we found a relationship between CSF markers of neurodegeneration, total tau and Aβ(1–42) and CSF orexin A concentrations. Our study provides evidence of an orexinergic dysfunction in bvFTD, correlating with several clinical symptoms. Further larger studies are needed to confirm our data. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-021-05250-x

Effect of short-term dietary intervention and probiotic mix supplementation on the gut microbiota of elderly obese women

Accumulating literature is providing evidence that the gut microbiota is involved in metabolic disorders, but the question of how to effectively modulate it to restore homeostasis, especially in the elderly, is still under debate. In this study, we profiled the intestinal microbiota of 20 elderly obese women (EO) at the baseline (T0), after 15 days of hypocaloric Mediterranean diet administered as part of a nutritional-metabolic rehabilitation program for obesity (T1), and after a further 15 days of the same diet supplemented with a probiotic mix (T2). Fecal samples were characterized by Illumina MiSeq sequencing of the 16S rRNA gene. The EO microbiota showed the typical alterations found in obesity, namely, an increase in potential pro-inflammatory components (i.e., Collinsella) and a decrease in health-promoting, short-chain fatty acid producers (i.e., Lachnospiraceae and Ruminococcaceae members), with a tendency to reduced biodiversity. After 15 days of the rehabilitation program, weight decreased by (2.7 \ub1 1.5)% and the gut microbiota dysbiosis was partially reversed, with a decline of Collinsella and an increase in leanness-related taxa. During the next 15 days of diet and probiotics, weight dropped further by (1.2 \ub1 1.1)%, markers of oxidative stress improved, and Akkermansia, a mucin degrader with beneficial effects on host metabolism, increased significantly. These findings support the relevant role of a correct dietetic approach, even in the short term, to modulate the EO gut microbiota towards a metabolic health-related configuration, counteracting the increased risk of morbidity in these patients

Comparison of Protein- or Amino Acid-Based Supplements in the Rehabilitation of Men with Severe Obesity: A Randomized Controlled Pilot Study

Background: Weight loss is associated with a reduction in all body compartments, including muscle mass (MM), and this effect produces a decrease in function and muscle strength. Our objective was to assess the impact of protein or amino acid supplements on MM loss in middle-aged men (age 35 kg/m2) during weight loss. Materials and Methods: We conducted a single-site randomized controlled trial (Clinicaltrials.gov NCT05143398) with 40 in-patient male subjects with severe obesity. Participants underwent an intervention program consisting of a low-calorie balanced diet and structured physical activity. They were randomly assigned to 4-week treatment groups: (1) control (CTR, N = 10), (2) protein (P, N = 10), (3) branched-chain amino acid (BCAA, N = 10), and (4) essential amino acid mixture with tricarboxylic acid cycle intermediates (PD-E07, N = 10) supplementation. Results: Following 4 weeks of intervention, all groups showed similar reductions in body weight compared to baseline. When examining the delta values, a notable increase in muscle mass (MM) was observed in the PD-E07 intervention group [MM (kg): 2.84 ± 3.57; MM (%): 3.63 ± 3.14], in contrast to the CTR group [MM (kg): −2.46 ± 3.04; MM (%): −0.47 ± 2.28], with a statistical significance of p = 0.045 and p = 0.023, respectively. However, the MM values for the P group [MM (kg): −2.75 ± 5.98, p = 0.734; MM (%): −0.44 ± 4.02, p = 0.990] and the BCAA group [MM (kg): −1 ± 3.3, p = 0.734; MM (%): 0.34 ± 2.85, p = 0.956] did not exhibit a statistically significant difference when compared to the CTR group. Conclusions: Amino acid-based supplements may effectively mitigate the loss of MM typically observed during weight reduction. Further validation through large-scale studies is necessary

Taurine administration recovers motor and learning deficits in an angelman syndrome mouse model

Angelman syndrome (AS, MIM 105830) is a rare neurodevelopmental disorder affecting 1:10\ue2\u80\u9320,000 children. Patients show moderate to severe intellectual disability, ataxia and absence of speech. Studies on both post-mortem AS human brains and mouse models revealed dysfunctions in the extra synaptic gamma-aminobutyric acid (GABA) receptors implicated in the pathogenesis. Taurine is a free intracellular sulfur-containing amino acid, abundant in brain, considered an inhibiting neurotransmitter with neuroprotective properties. As taurine acts as an agonist of GABA-A receptors, we aimed at investigating whether it might ameliorate AS symptoms. Since mice weaning, we orally administered 1 g/kg/day taurine in water to Ube3a-deficient mice. To test the improvement of motor and cognitive skills, Rotarod, Novel Object Recognition and Open Field tests were assayed at 7, 14, 21 and 30 weeks, while biochemical tests and amino acid dosages were carried out, respectively, by Western-blot and high-performance liquid chromatography (HPLC) on frozen whole brains. Treatment of Ube3am\ue2\u80\u93/p+mice with taurine significantly improved motor and learning skills and restored the levels of the post-synaptic PSD-95 and pERK1/2-ERK1/2 ratio to wild type values. No side effects of taurine were observed. Our study indicates taurine administration as a potential therapy to ameliorate motor deficits and learning difficulties in AS

Acute vitamin D3 supplementation in severe obesity : evaluation of multimeric adiponectin

Obesity predisposes to vitamin D deficiency (VDD) and glucose abnormalities. It is currently debated if vitamin D administration may improve glucose homeostasis by interacting with modulators of insulin sensitivity, such as adiponectin and its oligomers. In a 4-week inpatient study on a metabolic rehabilitation program, consisting of individualized caloric restriction and aerobic physical exercise in obese subjects with VDD, we assessed the acute effects of 600,000 IU cholecalciferol given per os VD group, 12 subjects, body mass index (BMI) 42.7 \uc2\ub1 1.3 kg/m2) or placebo per os (PL group, 12 subjects, BMI 39.8 \uc2\ub1 0.9 kg/m2) on high (HWM-A), medium (MMW-A), and low molecular weight adiponectin (LMW-A), as quantified by western immunoblot (WIB) and ELISA. During the 4-week study, dieting promoted a similar magnitude of weight loss in VD and PL groups. Compared to the PL group, cholecalciferol administration increased 25(OH)Vit D levels (p < 0.001) and promoted a significant increase of HMW-A expression analyzed by WIB (p = 0.02). In parallel, a significant decrease of leptin/HMW-A ratio (p < 0.05), a biomarker of metabolic homeostasis, was observed. During the study, changes of MMW-A and LMW-A occurred independently of cholecalciferol administration, and were likely explained by weight loss. At odds with these findings, the ELISA assessment of adiponectin oligomers showed no modifications in the VD group or PL group. Current findings suggest that acute cholecalciferol administration selectively modifies HMW-A and the leptin/HMW-A ratio

Type 2 diabetes and metabolic syndrome are associated with increased expression of 11beta-hydroxysteroid dehydrogenase 1 in obese subjects

Objective: The role of glucocorticoids production in adipose tissue in the development of metabolic disorders in humans has not been fully characterized. We investigated whether in obese subjects, 11\u3b2-hydroxysteroid dehydrogenase type 1 (11\u3b2-HSD1) expression in subcutaneous (SAT) and visceral (VAT) adipose tissue is associated with the occurrence of metabolic disorders and the expression of adiponectin and tumor necrosis factor \u3b1 (TNF\u3b1) and two glucocorticoid-regulated adipokines able to influence the metabolic control. Design and subjects: Sixty-two obese patients were enrolled in the study. SAT and VAT samples were obtained from 13 patients undergoing bariatric surgery (body mass index (BMI) 39.1\ub15.3 kg/m2). SAT samples were obtained from 49 patients who underwent periumbilical biopsy (BMI 36.9\ub15.1 kg/m2). Measurements: Oral glucose tolerance tests in subjects without known diabetes. Circulating glucose, lipid, insulin, adiponectin, TNF\u3b1 and urinary-free cortisol levels. Real-time PCR to quantify mRNA levels of 11\u3b2-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), adiponectin and TNF\u3b1. Western blot analysis to evaluate 11\u3b2-HSD1 protein expression. Results: In the majority of the obese subjects, VAT expresses more 11\u3b2-HSD1 than SAT. VAT 11\u3b2-HSD1 expression was not associated with metabolic disorders. SAT 11\u3b2-HSD1 mRNA levels were higher in subjects with than in those without metabolic syndrome (P<0.05) and in patients with type 2 diabetes compared to patients with impaired or normal glucose tolerance (P<0.0001). SAT 11\u3b2-HSD1 expression was independently related to fasting glucose (P<0.0001) and urinary-free cortisol levels (P<0.01), and increased expression of 11\u3b2-HSD1 was associated with increased adiponectin and TNF\u3b1 expression and decreased serum adiponectin levels (all P's <0.05). Conclusions: In obese subjects, increased 11\u3b2-HSD1 expression in SAT, but not in VAT, is associated with the worsening of metabolic conditions. We hypothesize that higher glucocorticoid production in adipose tissue would favor the development of metabolic disorders through a decrease in adiponectin release

Vascular Dynamics and Peripheral Oxygen Uptake in Obese Individuals during Progressive Physical Exercise.

Obese men show higher O2 consumption than lean men during physical exercise, with a trend toward higher peripheral O2 extraction; this is probably due to their larger muscle mass. The aim of this study was to examine this phenomenon by measuring 2 vasoactive substances, endothelin-1 (ET-1) and nitric oxide (NO), during a progressive submaximal exercise. Seventeen obese (body mass index [BMI] 38.6) and 15 lean (BMI 22.5) men performed a maximal progressive cycle ergometer exercise to determine peak power output (PPO) and peak O2 consumption (V∙O2peak); thereafter, they performed a submaximal cycle ergometer incremental test (every 6 min) at the same percentage of V∙O2peak until they reached 57.5% PPO. Blood samples were collected at rest and at the end of every step to measure ET-1 and NO concentrations. At rest, the ET-1 and NO concentrations in obese men and lean controls were the same. However, during exercise, the ET-1 concentration at each step was significantly lower (p &lt; 0.05) in the obese group. There was no significant difference in NO concentration between the 2 groups, although the increase at the beginning of the exercise session was faster in obese individuals. During submaximal exercise, end-tidal O2 pressure (PETO2) was lower in the obese group, with a significant difference in the PETO2/fat-free mass ratio at each step. ET-1 and NO levels during physical exercise are different in obese versus lean men. This may support the notion that increased O2 consumption in obesity is due to different behaviors of the cardiorespiratory and circulatory systems

Effect of short-term dietary intervention and probiotic mix supplementation on the gut microbiota of elderly obese women

Accumulating literature is providing evidence that the gut microbiota is involved in metabolic disorders, but the question of how to effectively modulate it to restore homeostasis, especially in the elderly, is still under debate. In this study, we profiled the intestinal microbiota of 20 elderly obese women (EO) at the baseline (T0), after 15 days of hypocaloric Mediterranean diet administered as part of a nutritional-metabolic rehabilitation program for obesity (T1), and after a further 15 days of the same diet supplemented with a probiotic mix (T2). Fecal samples were characterized by Illumina MiSeq sequencing of the 16S rRNA gene. The EO microbiota showed the typical alterations found in obesity, namely, an increase in potential pro-inflammatory components (i.e., Collinsella) and a decrease in health-promoting, short-chain fatty acid producers (i.e., Lachnospiraceae and Ruminococcaceae members), with a tendency to reduced biodiversity. After 15 days of the rehabilitation program, weight decreased by (2.7 \ub1 1.5)% and the gut microbiota dysbiosis was partially reversed, with a decline of Collinsella and an increase in leanness-related taxa. During the next 15 days of diet and probiotics, weight dropped further by (1.2 \ub1 1.1)%, markers of oxidative stress improved, and Akkermansia, a mucin degrader with beneficial effects on host metabolism, increased significantly. These findings support the relevant role of a correct dietetic approach, even in the short term, to modulate the EO gut microbiota towards a metabolic health-related configuration, counteracting the increased risk of morbidity in these patients

Gut Microbiota and Fear Processing in Women Affected by Obesity: An Exploratory Pilot Study

The microbiota–gut–brain axis extends beyond visceral perception, influencing higher-order brain structures, and ultimately psychological functions, such as fear processing. In this exploratory pilot study, we attempted to provide novel experimental evidence of a relationship between gut microbiota composition and diversity, and fear-processing in obesity, through a behavioral approach. Women affected by obesity were enrolled and profiled for gut microbiota, through 16S rRNA amplicon sequencing. Moreover, we tested their ability to recognize facial fearful expressions through an implicit-facial-emotion-recognition task. Finally, a traditional self-report questionnaire was used to assess their temperamental traits. The participants exhibited an unbalanced gut microbiota profile, along with impaired recognition of fearful expressions. Interestingly, dysbiosis was more severe in those participants with altered behavioral performance, with a decrease in typically health-associated microbes, and an increase in the potential pathobiont, Collinsella. Moreover, Collinsella was related to a lower expression of the persistence temperamental trait, while a higher expression of the harm-avoidance temperament, related to fear-driven anxiety symptoms, was linked to Lactobacillus. Once confirmed, our findings could pave the way for the design of innovative microbiome-based strategies for the treatment of psychological and emotional difficulties by mitigating obesity-related consequences and behaviors

Mental flexibility assessment: A research protocol for patients with Parkinson's Disease and Anorexia Nervosa

Mental Flexibility oscillates between adaptive variability in behavior and the capacity to restore homeostasis, linked to mental health. It has recently been one of the most investigated abilities in mental and neurological diseases such as Anorexia nervosa and Parkinson's disease, studied for rigidity or cognitive inflexibility. Patients with anorexia nervosa have rigid cognitive processes about food and weight, which leads to restrictive eating and excessive exercise. People who struggle to adapt their cognitive processes and actions to change their diet and exercise habits may have a harder time recovering from the disorder. On the other hand, research suggests that Parkinson's disease patients may have cognitive flexibility impairments that impair their ability to perform daily tasks and adapt to new environments. Although of clinical interest, mental flexibility lacks theoretical liberalization and unified assessment. This study introduces "IntellEGO"a protocol for a new, multidimensional psychometric assessment of flexibility. This assessment evaluates a person's authentic ability to handle daily challenges using cognitive, emotional, and behavioral factors. Since traditional assessments often focus on one domain, we aim to examine flexibility from multiple angles, acknowledging the importance of viewing people as whole beings with mental and physical aspects. The study protocol includes two assessment phases separated by a rehabilitation period. T0, the acute phase upon admission, and T1, the post-rehabilitation phase lasting 15 days for Parkinson's patients and 4 weeks for eating disorder patients, will be assessed. Neuropsychological performance, self-report questionnaires, psychophysiological measures, and neuroendocrine measures will be collected from Anorexia Nervosa and Parkinson's Disease patients during each study phase. The objective of this procedure is to provide clinicians with a comprehensive framework for conducting meticulous assessments of mental flexibility. This framework considers emotional, cognitive, and behavioral factors, and is applicable to various patient populations