The Effect of Obesity Class on the Energetics and Mechanics of Walking

Higher mass-normalized net energy cost of walking (NetCw/kg) and mechanical pendular recovery are observed in obese compared to lean adults. This study aimed to investigate the effect of different classes of obesity on the energetics and mechanics of walking and to explore the relationships between body mass, NetCw/kg and gait mechanics by using principal component analysis (PCA). NetCw/kg and gait mechanics were computed in severely obese (SOG; n = 18, BMI = 40.1 ± 4.4 kg·m−2), moderately obese (MOG; n = 17, BMI = 32.2 ± 1.5 kg·m−2) and normal-weight (NWG; n = 13, BMI = 22.0 ± 1.5 kg·m−2) adults during five walking trials (0.56, 0.83, 1.11, 1.39, 1.67 m·s−1) on an instrumented treadmill. NetCw/kg was significantly higher in SOG compared to NWG (p = 0.019), with no significant difference between SOG and MOG (p = 0.14), nor between MOG and NWG (p = 0.27). Recovery was significantly higher in SOG than in NWG (p = 0.028), with no significant difference between SOG and MOG (p = 0.13), nor between MOG and NWG (p = 0.35). PCA models explained between 17.0% and 44.2% of the data variance. This study showed that: (1) obesity class influences the gait energetics and mechanics; (2) PCA was able to identify two components, showing that the obesity class is associated with lower walking efficiency and better pendulum-like characteristics.

Effects of a 3-Week Hospital-Controlled Very-Low-Calorie Diet in Severely Obese Patients

Although a very-low-calorie diet (VLCD) is considered safe and has demonstrated benefits among other types of diets, data are scarce concerning its effects on improving health and weight loss in severely obese patients. As part of the personalized weight loss program developed at the Duga Resa Special Hospital for Extended Treatment, Croatia, we evaluated anthropometric, biochemical, and permanent DNA damage parameters (assessed with the cytochalasin B-blocked micronucleus cytome assay—CBMN) in severely obese patients (BMI ≥ 35 kg m−2) after 3-weeks on a 567 kcal, hospital-controlled VLCD. This is the first study on the permanent genomic (in)stability in such VLCD patients. VLCDs caused significant decreases in weight (loss), parameters of the lipid profile, urea, insulin resistance, and reduced glutathione (GSH). Genomic instability parameters were lowered by half, reaching reference values usually found in the healthy population. A correlation was found between GSH decrease and reduced DNA damage. VLCDs revealed susceptible individuals with remaining higher DNA damage for further monitoring. In a highly heterogeneous group (class II and III in obesity, differences in weight, BMI, and other categories) consisting of 26 obese patients, the approach demonstrated its usefulness and benefits in health improvement, enabling an individual approach to further monitoring, diagnosis, treatment, and risk assessment based on changing anthropometric/biochemical VLCD parameters, and CBMN results.

Lipidomic and Metabolomic Signature of Progression of Chronic Kidney Disease in Patients with Severe Obesity

Severe obesity is a major risk for chronic kidney disease (CKD). Early detection and careful monitoring of renal function are critical for the prevention of CKD during obesity, since biopsies are not performed in patients with CKD and diagnosis is dependent on the assessment of clinical parameters. To explore whether distinct lipid and metabolic signatures in obesity may signify early stages of pathogenesis toward CKD, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-high resolution accurate mass-mass spectrometry (GC-HRAM-MS) analyses were performed in the serum and the urine of severely obese patients with and without CKD. Moreover, the impact of bariatric surgery (BS) in lipid and metabolic signature was also studied, through LC-MS and GC-HRAM-MS analyses in the serum and urine of patients with severe obesity and CKD before and after undergoing BS. Regarding patients with severe obesity and CKD compared to severely obese patients without CKD, serum lipidome analysis revealed significant differences in lipid signature. Furthermore, serum metabolomics profile revealed significant changes in specific amino acids, with isoleucine and tyrosine, increased in CKD patients compared with patients without CKD. LC-MS and GC-HRAM-MS analysis in serum of patients with severe obesity and CKD after BS showed downregulation of levels of triglycerides (TGs) and diglycerides (DGs) as well as a decrease in branched-chain amino acid (BCAA), lysine, threonine, proline, and serine. In addition, BS removed most of the correlations in CKD patients against biochemical parameters related to kidney dysfunction. Concerning urine analysis, hippuric acid, valine and glutamine were significantly decreased in urine from CKD patients after surgery. Interestingly, bariatric surgery did not restore all the lipid species, some of them decreased, hence drawing attention to them as potential targets for early diagnosis or therapeutic intervention. Results obtained in this study would justify the use of comprehensive mass spectrometry-based lipidomics to measure other lipids aside from conventional lipid profiles and to validate possible early markers of risk of CKD in patients with severe obesity.

The Effectiveness of Extra Virgin Olive Oil and the Traditional Brazilian Diet in Reducing the Inflammatory Profile of Individuals with Severe Obesity: A Randomized Clinical Trial

We analyzed the effectiveness of two nutritional interventions alone and together, EVOO and the DieTBra, on the inflammatory profile of severely obese individuals. This study was an RCT with 149 individuals aged from 18 to 65 years, with a body mass index ≥ 35 kg/m2, randomized into three intervention groups: (1) 52 mL/day of EVOO (n = 50); (2) DieTBra (n = 49); and (3) DieTBra plus 52 mL/day of EVOO (DieTBra + EVOO, n = 50). The primary outcomes we measured were the-neutrophil-to-lymphocyte ratio (NLR) and the secondary outcomes we measured were the lymphocyte-to-monocyte ratio (LMR); leukocytes; and C reactive protein (CRP). After 12 weeks of intervention, DieTBra + EVOO significantly reduced the total leucocytes (p = 0.037) and LMR (p = 0.008). No statistically significant differences were found for the NLR in neither the intra-group and inter-group analyses, although a slight reduction was found in the DieTBra group (−0.22 ± 1.87). We observed reductions in the total leukocytes and LMR in the three groups, though without statistical difference between groups. In conclusion, nutritional intervention with DietBra + EVOO promotes a significant reduction in inflammatory biomarkers, namely leukocytes and LMR. CRP was reduced in EVOO and DieTBra groups and NLR reduced in the DieTBra group. This study was registered at ClinicalTrials.gov under NCT02463435.

Predicting novel candidate human obesity genes and their site of action by systematic functional screening in Drosophila

The discovery of human obesity-associated genes can reveal new mechanisms to target for weight loss therapy. Genetic studies of obese individuals and the analysis of rare genetic variants can identify novel obesity-associated genes. However, establishing a functional relationship between these candidate genes and adiposity remains a significant challenge. We uncovered a large number of rare homozygous gene variants by exome sequencing of severely obese children, including those from consanguineous families. By assessing the function of these genes in vivo in Drosophila, we identified 4 genes, not previously linked to human obesity, that regulate adiposity (itpr, dachsous, calpA, and sdk). Dachsous is a transmembrane protein upstream of the Hippo signalling pathway. We found that 3 further members of the Hippo pathway, fat, four-jointed, and hippo, also regulate adiposity and that they act in neurons, rather than in adipose tissue (fat body). Screening Hippo pathway genes in larger human cohorts revealed rare variants in TAOK2 associated with human obesity. Knockdown of Drosophila tao increased adiposity in vivo demonstrating the strength of our approach in predicting novel human obesity genes and signalling pathways and their site of action.