ABSTRACT
Skin pigmentation is paused after sun exposure; however, the mechanism behind this pausing is unknown. In this study, we found that the UVB-induced DNA repair system, led by the ataxia telangiectasia mutated (ATM) protein kinase, represses MITF transcriptional activity of pigmentation genes while placing MITF in DNA repair mode, thus directly inhibiting pigment production. Phosphoproteomics analysis revealed ATM to be the most significantly enriched pathway among all UVB-induced DNA repair systems. ATM inhibition in mouse or human skin, either genetically or chemically, induces pigmentation. Upon UVB exposure, MITF transcriptional activation is blocked owing to ATM-dependent phosphorylation of MITF on S414, which modifies MITF activity and interactome toward DNA repair, including binding to TRIM28 and RBBP4. Accordingly, MITF genome occupancy is enriched in sites of high DNA damage that are likely repaired. This suggests that ATM harnesses the pigmentation key activator for the necessary rapid, efficient DNA repair, thus optimizing the chances of the cell surviving. Data are available from ProteomeXchange with the identifier PXD041121.
Subject(s)
Ataxia Telangiectasia , Humans , Animals , Mice , Skin Pigmentation/genetics , DNA Repair , Ataxia Telangiectasia Mutated Proteins/genetics , Ataxia Telangiectasia Mutated Proteins/metabolism , Signal Transduction , DNA Damage , Phosphorylation , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolismABSTRACT
BACKGROUND: The effect of weight reduction following bariatric surgery is already well known. OBJECTIVES: To investigate the effects of abdominoplasty on metabolic markers indicative of weight loss. METHODS: The authors prospectively enrolled consecutive obese patients after laparoscopic sleeve gastrectomy. They were candidates for post-bariatric surgery abdominoplasty. The authors measured metabolic markers one day prior to surgery, 24 hours after, and 3 months following surgery. They recorded medical and demographic parameters. RESULTS: Sixteen patients were recruited for participation in the study. Mean age was 47 years and 88% of the patients were female. Bariatric surgery achieved a mean decline in body mass index of 13.8 kg/m2. All patients underwent abdominoplasty. Leptin and insulin levels were slightly increased at 3 months postoperative. No significant changes were observed in glucose, hemoglobin, or triglycerides throughout the study. CONCLUSIONS: In a cohort of obese patients undergoing laparoscopic sleeve gastrectomy followed by abdominoplasty, no significant changes were noted in a patient's metabolic profiles. The results suggest that abdominoplasty has no effect on the metabolic markers tested in contrast to other reports; however, the cosmetic, behavioral, and psychological advantages of abdominoplasty are well established.
Subject(s)
Abdominoplasty , Bariatric Surgery , Gastrectomy , Insulin/metabolism , Leptin/metabolism , Obesity/surgery , Weight Loss , Adult , Bariatric Surgery/methods , Cohort Studies , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVES: To present the results of bariatric surgery performed in the elderly population at the Wolfson Medical Center. METHODS: The study population consisted of all elderly patients (aged 65 years and older) who had undergone bariatric surgery between 2009 and 2016. Data was collected from the medical records and by a phone questionnaire. The percentage of excess BMI lost (%EBMIL) was the percentage of BMI lost after the surgery, out of the target BMI of 27 kg/m2. Improvement of obesity related co-morbidities was defined as the decrease in the number of medications and/or dosage, or remission. RESULTS: Forty eight patients aged 65 years or older underwent bariatric surgery during the study acquisition period (mean age 67.9±2.8 years, 60% females). The types of surgery performed were: laparoscopic sleeve gastrectomy (LSG, 79%), mini gastric bypass, (MGB, 17%), and Roux and Y gastric bypass (RYGB, 4%). The weight decreased significantly (average BMI units lost was 9.4±5.6 units, p<0.001), and the mean EBWL% was 66.8±32.5%. The surgery was also very effective in improving co-morbidities: DM-65.2%, HTN-54.3%, hyperlipidemia-40%. After a follow-up period longer than 4.2 years the failure rate (EBWL<50%) was 53.3%, however, these patients still presented a lower postoperative weight. All the patients who failed underwent LSG. CONCLUSIONS: Bariatric surgery is very effective in terms of long term weight loss in the geriatric patient.
