Obesity drives adipose-derived stem cells into a senescent and dysfunctional phenotype associated with P38MAPK/NF-KB axis.

BACKGROUND: Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control. RESULTS: Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21WAF1/Cip1) up-regulation. We also observed increased senescence-associated ß-galactosidase (SA-ß-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16INK4A) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli. CONCLUSIONS: Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis.

Weight-loss interventions and gut microbiota changes in overweight and obese patients: a systematic review.

Imbalances in the gut microbiota, the bacteria that inhabit the intestines, are central to the pathogenesis of obesity. This systematic review assesses the association between the gut microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity. This review identified 43 studies using the keywords 'overweight' or 'obesity' and 'microbiota' and related terms; among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation. The studies differed in their methodologies as well as their intervention lengths. Restrictive diets decreased the microbiota abundance, correlated with nutrient deficiency rather than weight loss and generally reduced the butyrate producers Firmicutes, Lactobacillus sp. and Bifidobacterium sp. The impact of surgical intervention depended on the given technique and showed a similar effect on butyrate producers, in addition to increasing the presence of the Proteobacteria phylum, which is related to changes in the intestinal absorptive surface, pH and digestion time. Probiotics differed in strain and duration with diverse effects on the microbiota, and they tended to reduce body fat. Prebiotics had a bifidogenic effect and increased butyrate producers, likely due to cross-feeding interactions, contributing to the gut barrier and improving metabolic outcomes. All of the interventions under consideration had impacts on the gut microbiota, although they did not always correlate with weight loss. These results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long-term detrimental effects on the colon. In contrast, prebiotics might restore a healthy microbiome and reduce body fat.

Importance of musculoskeletal pain in work activities in obese individuals.

BACKGROUND: The consequences of obesity include musculoskeletal pain and its influence on a person's social, personal, and professional life, which is a great challenge for the multidisciplinary team in the treatment of obesity. The objective of this work was to evaluate musculoskeletal pain in the work activities of obese individuals. METHODS: An uncontrolled cross-sectional study was conducted. During 8 months, all obese individuals seen in the preoperative period at a tertiary care referral center for the treatment of obesity and metabolic syndrome were invited to participate in the study. Ninety-five persons filled out the Nordic questionnaire for the analysis of musculoskeletal symptoms (Nordic musculoskeletal questionnaire (NMQ)) after having signed an informed consent form and having met the inclusion criteria of the study. RESULTS: Of the 95 patients assessed, 71 were females, the mean age was 39.3 ± 10.1 years, and mean body mass index was 47.25 ± 8.72 kg/m(2). Sixty-three (66.31 %) individuals felt musculoskeletal pain in some region of the body in the last 12 months, and 42 (44.21 %) sometimes gave up working in the same period because of musculoskeletal pain. There was a statistical association between BMI and the three aspects evaluated by the NMQ. CONCLUSIONS: Musculoskeletal pain was very related to obese individuals who participated in this study, and in the majority cases, execution of the work activities of these persons was impeded. This indicates a need for further studies that address this subject to better attend to and intervene in the health of this population.

Functioning of obese individuals in pre- and postoperative periods of bariatric surgery.

BACKGROUND: Obesity is a pathologic condition that causes functional incapacity, with reduction of quality of life and life expectancy and an increase in mortality. Bariatric surgery is indicated to alleviate associated comorbidities and increase physical capacity. The objective of this work was to evaluate the functional capacity of patients with morbid obesity before and after (3 months) bariatric surgery. METHODS: This was a cross-sectional study involving 67 patients, where 61 were women and six men, with a mean age of 38 ± 10 years and mean BMI of 50.45 ± 8.5 kg/m2. All patients were assessed before surgery and 3 months afterwards. The following assessments were performed: 6-min walk test (6MWT), functional independence measure (FIM), and test for risk of falling and transfer capacity, called the timed up-and-go test. RESULTS: The study demonstrated a reduction in parameters evaluated in 6MWT with a statistically significant difference at two times (rest and final) when evaluated before and after bariatric surgery (p < 0.001). In relation to the FIM and timed up-and-go test, the patients showed a statistically significant improvement (p < 0.001) for both when comparing the tasks evaluated at the pre- and postoperative moments. CONCLUSIONS: Obesity has an impact on the functioning and quality of life of patients. We observed an improvement in all instruments used for assessment before and after bariatric surgery, where a linear component was demonstrated in relation to diminution of body mass index and functioning.

Economic benefits of bariatric surgery.

With the high prevalence of obesity and associated comorbidities, the costs of health services produce a great economic impact. The objective of this work was to evaluate the economic benefits of bariatric surgery and to relate the costs to the impact on the health of the individual. A historic cohort study was conducted, with review of medical charts of 194 patients who fulfilled the inclusion criteria for the study. The costs for medications, professional care, and examinations in the pre- and postoperative periods were analyzed, taking into consideration the comorbidities DM2, SAH, and dyslipidemia. The study demonstrated a reduction in the medical costs in the course of the postoperative period, in relation to expenses for medications, professional care, and examinations in the preoperative period. Comparing the preoperative expenses with different times in the postoperative period, a statistically significant difference was seen at all time evaluated (p < 0.001). The resolution of comorbidities was higher than 95% at 36 months after surgery. No statistically significant difference was seen with respect to the prevalence of comorbidities between the sexes in the pre- and postoperative periods (p > 0.05). With regard to age, younger patients showed lower rates of comorbidities in the pre- and postoperative periods (p < 0.001). The costs of the surgery are high, but the expenditures for medications, professional care, and examinations decrease progressively after the operation, where this is more evident in patients with more associated comorbidities.