Purpose
A multifold association relates the hypothalamo-pituitary-thyroid axis to body weight. The potential underlying mechanisms are incompletely understood. Further, the mild severity of obesity ...and the small proportion of individuals with obesity in so far published cohort studies provide little insights on metabolic correlates of thyroid function in obesity.
Methods
We retrospectively enrolled 5009 adults with obesity (F/M, 3448/1561; age range, 18-87 years; BMI range, 30.0-82.7 kg/m
2
), without known thyroid disease in a study on TSH and fT4 levels, lipid profile, glucose homeostasis and insulin resistance, anthropometric parameters including BIA-derived fat mass (%FM) and fat-free mass (FFM).
Results
The overall reference interval for TSH in our obese cohort was 0.58-5.07 mIU/L. As subgroups, females and non-smokers showed higher TSH levels as compared to their counterparts (p<0.0001 for both), while fT4 values were comparable between groups. There was a significant upward trend for TSH levels across incremental BMI classes in females, while the opposite trend was seen for fT4 levels in males (p<0.0001 for both). Expectedly, TSH was associated with %FM and FFM (p<0,0001 for both). TSH and fT4 showed correlations with several metabolic variables, and both declined with aging (TSH, p<0.0001; fT4, p<0.01). In a subgroup undergoing leptin measurement, leptin levels were positively associated with TSH levels (p<0.01). At the multivariable regression analysis, in the group as a whole, smoking habit emerged as the main independent predictor of TSH (β=-0.24, p<0.0001) and fT4 (β=-0.25, p<0.0001) levels. In non-smokers, %FM (β=0.08, p<0.0001) and age (β=-0.05, p<0.001) were the main significant predictors of TSH levels. In the subset of nonsmokers having leptin measured, leptin emerged as the strongest predictor of TSH levels (β=0.17, p<0.01).
Conclusions
Our study provides evidence of a gender- and smoking-dependent regulation of TSH levels in obesity.
Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited tumor syndrome, associated with parathyroid, pituitary, and gastro-entero-pancreatic (GEP) neuroendocrine tumors ...(NETs). MEN1 is usually consequent to different germline and somatic mutations of the
tumor suppressor gene, although phenocopies have also been reported. This review analyzed main biomedical databases searching for reports on
gene mutations and focused on aggressive and aberrant clinical manifestations to investigate the potential genotype-phenotype correlation. Despite efforts made by several groups, this link remains elusive to date and evidence that aggressive or aberrant clinical phenotypes may be related to specific mutations has been provided by case reports and small groups of MEN1 patients or families. In such context, a higher risk of aggressive tumor phenotypes has been described in relation to frameshift and non-sense mutations, and predominantly associated with aggressive GEP NETs, particularly pancreatic NETs. In our experience a novel heterozygous missense mutation at
in exon 6 was noticed in a MEN1 patient operated for macro-prolactinoma, who progressively developed recurrent parathyroid adenomas, expanding gastrinomas and, long after the first MEN1 manifestation, a neuroendocrine uterine carcinoma. In conclusion, proof of genotype-phenotype correlation is limited but current evidence hints at the need for long-term interdisciplinary surveillance in patients with aggressive phenotypes and genetically confirmed MEN1.
ANGPTL8 is a liver-derived protein related to insulin-sensitivity. Its relationship with obesity and liver function in Prader-Willi syndrome (PWS) is unknown. The present study investigated ...circulating ANGPTL8 in PWS and controls with common obesity, assessing its association to liver steatosis. For this purpose, 20 obese PWS and 20 controls matched for body mass index (BMI), sex and age underwent analysis of ANGPTL8 levels, glucose and lipid metabolism. Liver function tests and degree of liver steatosis by ultrasonography (US), fat-free mass (FFM) and fat mass (FM) by dual-energy x-ray absorptiometry (DEXA) were also assessed. In comparison to controls, obese PWS showed lower values of FFM (p < 0.0001) and higher FM (p = 0.01), while harbouring higher HDL cholesterol, lower triglycerides and OGTT-derived insulin levels, as well as a lower prevalence and severity of liver steatosis. With respect to obese controls, ANGPTL8 levels were significantly lower in PWS (p = 0.007) and overall correlated with transaminase levels and the severity of liver steatosis, as well as FFM (p < 0.05 for all). By a stepwise multivariable regression analysis, ANGPTL8 levels were independently predicted by PWS status (p = 0.01) and liver steatosis (p < 0.05). In conclusion, ANGPTL8 levels are lower in PWS than obese controls and are inversely associated with the severity of liver steatosis. Further studies should investigate the potential genetic basis for this observation.
In clinical practice, there is the diffuse conviction that obese subjects with metabolic syndrome may be more difficult to treat.
The aim of the present study was that to investigate the ...effectiveness of a 3-week in-hospital body weight reduction program (BWRP) in a large population of obese subjects with and without metabolic syndrome (
= 1922; 222 men and 1700 women, age range 18-83 yr). Outcomes such as body mass index (BMI), total (TOT) and HDL cholesterol, systolic and diastolic blood pressures (SBP and DBP, respectively), coronary heart disease (CHD) score, fatigue severity score (FSS), and stair climbing test (SCT) time were evaluated before and after the intervention (Δ). A sex-, BMI-, and age-related stratification of the obese population with or without metabolic syndrome was applied.
When compared to obese subjects without metabolic syndrome, at the basal conditions, obese subjects had a poorer cardiometabolic profile, as demonstrated by higher triglycerides, TOT-cholesterol, DBP, SBP, and CHD score, and a more compromised muscle performance (evaluated by SCT), associated with more perception of fatigue (measured by FSS). Nevertheless, obese subjects with metabolic syndrome obtained more benefits from BWRP than those without metabolic syndrome for some outcomes (i.e., ΔTOT-cholesterol, ΔSBP, and ΔCHD score). Despite these differences, the BWRP-induced weight loss was similar between the two groups (i.e., ΔBMI) as well as the gain of muscle performance (i.e., ΔSCT) and the reduction of fatigue (i.e., ΔFSS). Interestingly, the potentially deleterious fall in HDL-cholesterol levels after BWRP was less evident in obese subjects with metabolic syndrome than those without metabolic syndrome. When pooling all data, the ΔCHD score was associated with age, sex, and metabolic syndrome. The remaining outcomes, such as ΔBMI, ΔFSS, and ΔSCT time, were associated with sex and age but not with metabolic syndrome. Finally, ΔBMI was positively correlated with ΔCHD score, ΔFSS, and ΔSCT time in both obese subjects without metabolic syndrome and obese subjects with metabolic syndrome.
When comparing obese subjects undergoing a BWRP, metabolic syndrome is not a negative predictive factor affecting the effectiveness of this intervention in terms of weight loss, muscle performance, and psychological well-being.
Introduction
The study of taste functionality and its relation to human health is receiving growing attention. Obesity has been reported to cause alterations in sensory perception regarding system ...functionality and preferences. However, a small body of research addresses tastes perception and its modification with the achievement of body mass reduction through surgical intervention. Much fewer efforts have been made to evaluate the impact of mild restrictive nutritional intervention on gustatory functions. Thus, the objectives of this study were to determine if a dietary intervention of 4 weeks following a restricted balanced Mediterranean diet would affect the sweet and salty taste thresholds of subjects with severe obesity and could influence their anthropometric and blood parameters.
Methods
Fifty-one patients with severe obesity (
F
: 31; age: 43.7 ± 12.5; BMI = 47.6 ± 1.0) were enrolled in the study. The recognition threshold for sweet and salty taste and anthropometric and blood parameters were assessed before and after the 4-week weight loss program.
Results and Discussion
The Mediterranean diet has proven to be an effective treatment, significantly improving all anthropometric and blood parameters (
p
< 0.05) after 4 weeks of intervention. Moreover, the hypo-sodium treatment associated with the diet significantly improved the salty threshold (
p
< 0.001). No changes were detected for the sweet threshold. Collectively, these data highlight that dietary treatment might impact taste perception differently. Therefore, a taste-oriented nutritional intervention could represent a novel approach to developing more individualized, taste-oriented follow-up interventions to maintain sustainable and long-term weight loss.
The use of high-dimensional data has expanded in many fields, including in clinical research, thus making variable selection methods increasingly important compared to traditional statistical ...approaches. The work aims to compare the performance of three supervised Bayesian variable selection methods to detect the most important predictors among a high-dimensional set of variables and to provide useful and practical guidelines of their use. We assessed the variable selection ability of: (1) Bayesian Kernel Machine Regression (BKMR), (2) Bayesian Semiparametric Regression (BSR), and (3) Bayesian Least Absolute Shrinkage and Selection Operator (BLASSO) regression on simulated data of different dimensions and under three scenarios with disparate predictor-response relationships and correlations among predictors. This is the first study describing when one model should be preferred over the others and when methods achieve comparable results. BKMR outperformed all other models with small synthetic datasets. BSR was strongly dependent on the choice of its own intrinsic parameter, but its performance was comparable to BKMR with large datasets. BLASSO should be preferred only when it is reasonable to hypothesise the absence of synergies between predictors and the presence of monotonous predictor-outcome relationships. Finally, we applied the models to a real case study and assessed the relationships among anthropometric, biochemical, metabolic, cardiovascular, and inflammatory variables with weight loss in 755 hospitalised obese women from the Follow Up OBese patients at AUXOlogico institute (FUOBAUXO) cohort.
The treatment of obesity requires creating an energy deficit through caloric restriction and physical activity. Energy needs are estimated assessing the resting energy expenditure (REE) that in the ...clinical practice is estimated using predictive equations. In the present cross sectional study, we compared, in a large cohort of morbidly obese patients, the accuracy of REE predictive equations recommended by current obesity guidelines Harris-Benedict, WHO/FAO/ONU and Mifflin-St Jeor (MJ) and/or developed for obese patients (Muller, Muller BC, Lazzer, Lazzer BC), focusing on the effect of comorbidities on the accuracy of the equations. Data on REE measured by indirect calorimetry and body composition were collected in 4,247 obese patients (69% women, mean age 48 ± 19 years, mean BMI 44 ± 7 Kg/m
) admitted to the Istituto Auxologico Italiano from 1999 to 2014. The performance of the equations was assessed in the whole cohort, in 4 groups with 0, 1, 2, or ≥ 3 comorbidities and in a subgroup of 1,598 patients with 1 comorbidity (47.1% hypertension, 16.7% psychiatric disorders, 13.3% binge eating disorders, 6.1% endocrine disorders, 6.4% type 2 diabetes, 3.5% sleep apnoea, 3.1% dyslipidemia, 2.5% coronary disease). In the whole cohort of obese patients, as well as in each stratum of comorbidity number, the MJ equation had the highest performance for agreement measures and bias. The MJ equation had the best performance in obese patients with ≥3 comorbidities (accuracy of 61.1%, bias of -89.87) and in patients with type 2 diabetes and sleep apnoea (accuracy/bias 69%/-19.17 and 66%/-21.67 respectively), who also have the highest levels of measured REE. In conclusion, MJ equation should be preferred to other equations to estimate the energy needs of Caucasian morbidly obese patients when measurement of the REE cannot be performed. As even MJ equation does not precisely predict REE, it should be better to plan the diet intervention by measuring rather than estimating REE. Future studies focusing on the clinical differences that determine the high inter-individual variability of the precision of the REE predictive equations (e.g., on the organ-tissue metabolic rate), could help to develop predictive equations with a better performance.
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.
Among endogenous signaling networks involved in both rewarding and homeostatic mechanisms of obesity, a relevant role is played by the endocannabinoid (ECS) and the opioid (EOS) systems. We here ...studied the transcriptional regulation of ECS and EOS genes in the hypothalamus of Diet-induced obesity rats, a preclinical model of obesity, as well as in humans with obesity and healthy controls. A significant and selective increase in type 1 cannabinoid receptor gene (
) expression was observed at the beginning of obesity development (5 weeks on high fat diet) as well as after 21 weeks of high diet exposure. After 5 weeks on high fat diet, selective up-regulation of mu opioid receptor gene (
) expression was also observed. Consistently, epigenetic studies showed a selective and significant decrease in DNA methylation at specific CpG sites at both gene promoters in overweight rats, but only after 5 weeks on high fat diet. Moreover, significantly lower levels of DNA methylation were observed at selected CpG sites of both receptor gene promoters, analyzed in peripheral blood mononuclear cells from younger (<30 years old) humans with obesity, as well as in those with shorter time length from disease onset. Taken together, we here provide evidence of selective, synergistic and time-dependent transcriptional regulation of
and
genes in overweight rats, as well as in human subjects. These alterations in genes regulation could contribute to the development of the obese phenotype, and we thus suggest
and
epigenetic modulation as possible biomarkers of obesity development. Due to the reversible nature of the epigenetic hallmark, our data might also open new avenue to early environmental strategies of intervention.
Background. Peripheral fat tissue is known to positively influence bone health. However, evidence exists that the risk of non-vertebral fractures can be increased in postmenopausal women with obesity ...as compared to healthy controls. The role of sclerostin, the SOST gene protein product, and body composition in this condition is unknown. Methods. We studied 28 severely obese premenopausal (age, 44.7 ± 3.9 years; BMI, 46.0 ± 4.2 kg/m2) and 28 BMI-matched post-menopausal women (age, 55.5 ± 3.8 years; BMI, 46.1 ± 4.8 kg/m2) thorough analysis of bone density (BMD) and body composition by dual X-ray absorptiometry (DXA), bone turnover markers, sclerostin serum concentration, glucose metabolism, and a panel of hormones relating to bone health. Results. Postmenopausal women harbored increased levels of the bone turnover markers CTX and NTX, while sclerostin levels were non-significantly higher as compared to premenopausal women. There were no differences in somatotroph, thyroid and adrenal hormone across menopause. Values of lumbar spine BMD were comparable between groups. By contrast, menopause was associated with lower BMD values at the hip (p < 0.001), femoral neck (p < 0.0001), and total skeleton (p < 0.005). In multivariate regression analysis, sclerostin was the strongest predictor of lumbar spine BMD (p < 0.01), while menopausal status significantly predicted BMD at total hip (p < 0.01), femoral neck (p < 0.001) and total body (p < 0.05). Finally, lean body mass emerged as the strongest predictor of total body BMD (p < 0.01). Conclusions. Our findings suggest a protective effect of obesity on lumbar spine and total body BMD at menopause possibly through mechanisms relating to lean body mass. Given the mild difference in sclerostin levels between pre- and postmenopausal women, its potential actions in obesity require further investigation.
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