Moataz Bashah

Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients

Objective Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. Methods OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery. Levels of 4-HNE protein adducts, adipocyte size and number of macrophages were determined within these tissues by immunohistochemistry. Adipogenic capacity and gene expression profiles were assessed in preadipocytes derived from these tissues in relation to insulin resistance and in response to 4-HNE, metformin or combined metformin and insulin treatment. Results Preadipocytes isolated from insulin resistant (IR) and T2DM individuals exhibited lower adipogenesis, marked by upregulation of anti-adipogenic genes, compared to preadipocytes derived from insulin sensitive (IS) individuals. Impaired adipogenesis was also associated with increased 4-HNE levels, smaller adipocytes and greater macrophage presence in the adipose tissues. Within the T2DM group, preadipocytes from combined metformin and insulin treated subset showed better in vitro adipogenesis compared to metformin alone, which was associated with less presence of macrophages and 4-HNE in the adipose tissues. Treatment of preadipocytes in vitro with 4-HNE reduced their adipogenesis and increased proliferation, even in the presence of metformin, which was partially rescued by the presence of insulin. Conclusion This study reveals involvement of 4-HNE in the impaired OM adipogenesis-associated with insulin resistance and T2DM and provides a proof of concept that this impairment can be reversed by the synergistic action of insulin and metformin. Further studies are needed to evaluate involvement of 4-HNE in metabolically impaired abdominal adipogenesis and to confirm benefits of combined metformin-insulin therapy in T2DM patients.

Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance

Aims/hypothesisA subset of obese individuals remains insulin sensitive by mechanisms as yet unclear. The hypothesis that maintenance of normal subcutaneous (SC) adipogenesis accounts, at least partially, for this protective phenotype and whether it can be abrogated by chronic exposure to IL-6 was investigated.MethodsAdipose tissue biopsies were collected from insulin-sensitive (IS) and insulin-resistant (IR) individuals undergoing weight-reduction surgery. Adipocyte size, pre-adipocyte proportion of stromal vascular fraction (SVF)-derived cells, adipogenic capacity and gene expression profiles of isolated pre-adipocytes were determined, along with local in vitro IL-6 secretion. Adipogenic capacity was further assessed in response to exogenous IL-6 application.ResultsDespite being equally obese, IR individuals had significantly lower plasma leptin and adiponectin levels and higher IL-6 levels compared with age-matched IS counterparts. Elevated systemic IL-6 in IR individuals was associated with hyperplasia of adipose tissue-derived SVF cells, despite higher frequency of hypertrophied adipocytes. SC pre-adipocytes from these tissues exhibited lower adipogenic capacity accompanied by downregulation of PPARγ (also known as PPARG) and CEBPα (also known as CEBPA) and upregulation of GATA3 expression. Impaired adipogenesis in IR individuals was further associated with increased adipose secretion of IL-6. Treatment of IS-derived SC pre-adipocytes with IL-6 reduced their adipogenic capacity to levels of the IR group.Conclusions/interpretationObesity-associated insulin resistance is marked by impaired SC adipogenesis, mediated, at least in a subset of individuals, by elevated local levels of IL-6. Understanding the molecular mechanisms underlying reduced adipogenic capacity in IR individuals could help target appropriate therapeutic strategies aimed at those at greatest risk of insulin resistance and type 2 diabetes mellitus.

4-hydroxynonenal causes impairment of human subcutaneous adipogenesis and induction of adipocyte insulin resistance

Objective: Increased adipose production of 4‐hydroxynonenal (4‐HNE), a bioreactive aldehyde, directly correlates with obesity and insulin resistance. The aim of this study was to elucidate the impact of 4‐HNE in mediating adipocyte differentiation and function in two metabolically distinct obese groups; the insulin sensitive (IS) and the insulin resistant (IR). Methods: Subcutaneous (SC) adipose tissues were obtained from eighteen clinically well characterized obese premenopausal women undergoing weight reduction surgery. Cellular distribution of 4‐HNE in the form of protein adducts was determined by immunohistochemistry in addition to its effect on oxidative stress, cell growth, adipogenic capacity and insulin signaling in preadipocytes derived from the IS and IR participants. Results: 4‐HNE was detected in the SC adipose tissue in different cell types with the highest level detected in adipocytes and blood vessels. Short and long‐term in vitro treatment of SC preadipocytes with 4‐HNE caused inhibition of their growth and increased production of reactive oxygen species (ROS) and antioxidant enzymes. Repeated 4‐HNE treatment led to a greater reduction in the adipogenic capacity of preadipocytes from IS subjects compared to IR and caused dephosphorylation of IRS‐1 and p70S6K while activating GSK3&agr;/&bgr; and BAD, triggering an IR phenotype. Conclusion: These data suggest that 4‐HNE‐induced oxidative stress plays a role in the regulation of preadipocyte growth, differentiation and insulin signaling and may therefore contribute to adipose tissue metabolic dysfunction associated with insulin resistance. HIGHLIGHTSObesity increases 4‐HNE‐His adducts in SC adipose tissue adipocytes and blood vessels.Acute 4‐HNE treatment alters redox homeostasis in SC preadipocytes.Chronic 4‐HNE treatment impairs SC adipogenesis and induces insulin resistance.Chronic 4‐HNE treatment has a greater impact on preadipocytes from IS vs IR subjects.

Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) By American Society for Metabolic and Bariatric Surgery (ASMBS) and American College of Surgery (ACS)

Metabolic and bariatric surgery procedures provide highly effective solutions for durable weight loss. This helps in resolving obesity-related comorbidities and reducing mortality in the morbidly obese population. Therefore, more and more healthcare facilities are gearing up to meet the increasing demand for such services. In order to achieve a single national accreditation standard for bariatric surgery centers in the United States and Canada, the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) was started by combining the accreditation programs of the American College of Surgeons (ACS) and the American Society for Metabolic and Bariatric Surgery (ASMBS).

Solid Organ Infections: Rare Complications After Laparoscopic Sleeve Gastrectomy: a Report of Four Cases

BackgroundLaparoscopic sleeve gastrectomy (LSG) is gaining popularity for the treatment of morbid obesity. It is a simple, low-cost procedure resulting in significant weight loss within a short period of time. LSG is a safe procedure with a low complication rate. The most significant complications are staple-line bleeding, stricture, and staple-line leak. Formation of liver and splenic abscesses is an extremely rare consequence of LSG. Liver abscess has been reported in one case report while splenic abscess has been reported in five case reports after LSG.MethodsThis study is a case report and literature review.ResultsWe report two cases of a pyogenic liver abscesses and two cases of splenic abscesses after LSG.ConclusionsAs LSG becomes more popular, clinicians need to be aware of uncommon but potentially serious complications related to it.