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Obesity promotes insulin resistance associated with liver inflammation, elevated glucose production, and type 2 diabetes. Although insulin resistance is attenuated in genetic mouse models that suppress systemic inflammation, it is not clear whether local resident macrophages in liver, denoted Kupffer cells (KCs), directly contribute to this syndrome. We addressed this question by selectively silencing the expression of the master regulator of inflammation, NF-κB, in KCs in obese mice. We used glucan-encapsulated small interfering RNA particles (GeRPs) that selectively silence gene expression in macrophages in vivo. Following intravenous injections, GeRPs containing siRNA against p65 of the NF-κB complex caused loss of NF-κB p65 expression in KCs without disrupting NF-κB in hepatocytes or macrophages in other tissues. Silencing of NF-κB expression in KCs in obese mice decreased cytokine secretion and improved insulin sensitivity and glucose tolerance without affecting hepatic lipid accumulation. Importantly, GeRPs had no detectable toxic effect. Thus, KCs are key contributors to hepatic insulin resistance in obesity and a potential therapeutic target for metabolic disease. [ABSTRACT FROM AUTHOR]

Purpose of Review: Roux-en-Y gastric bypass (RYGB) leads to remission of type 2 diabetes mellitus (T2DM) in a majority of patients. This is prompting investigation of RYGB, and other bariatric operations as interventional therapies for T2DM., Recent Findings: The impact of RYGB is due to an increase in the release of gastrointestinal hormones in response to a meal [glucagon-like peptide, peptide YY, oxyntomodulin]. This effect involves the parasympathetic nervous system. These same hormones are responsible for an early increase in β-cell secretion of insulin, leading to early remission of T2DM following RYGB. Progressive weight loss leads to a later improvement in peripheral insulin sensitivity, which is required for later remissions, and is responsible for re-emergence of T2DM in individuals who regain weight in long-term follow-up. As the success of bariatric surgery has prompted the emergence of the concept that T2DM is reversible, we offer a theory to predict reversibility of diabetes after bariatric surgery that is based on baseline beta cell function., Summary: This review will improve the understanding of the physiology of bariatric surgery and its impact on T2DM, stimulate investigations into new avenues to treat T2DM, and allow better selection of nonobese individuals for interventional therapy of T2DM.

Background: Adipose tissue expands in response to excess caloric intake, but individuals prone to deposit visceral instead of subcutaneous adipose tissue have higher risk of metabolic disease. The role of angiogenesis in the expandability of human adipose tissue depots is unknown. The objective of this study was to measure angiogenesis in visceral and subcutaneous adipose tissue and to establish whether there is a relationship between obesity, metabolic status, and the angiogenic properties of these depots., Methods and Results: Angiogenic capacity was determined by quantifying capillary branch formation from human adipose tissue explants embedded in Matrigel, and capillary density was assessed by immunohistochemistry. Subcutaneous adipose tissue had a greater angiogenic capacity than visceral tissue, even after normalization to its higher initial capillary density. Gene array analyses revealed significant differences in expression of angiogenic genes between depots, including an increased subcutaneous expression of angiopoietin-like protein 4, which is proangiogenic in an adipose tissue context. Subcutaneous capillary density and angiogenic capacity decreased with morbid obesity, and subcutaneous, but not visceral, adipose tissue angiogenic capacity correlated negatively with insulin sensitivity., Conclusions: These data imply that subcutaneous adipose tissue has a higher capacity to expand its capillary network than visceral tissue, but this capacity decreases with morbid obesity. The decrease correlates with insulin resistance, suggesting that impairment of subcutaneous adipose tissue angiogenesis may contribute to metabolic disease pathogenesis.

Purpose: The purpose of this study was to review the etiology and computed tomography (CT) findings of small-bowel obstruction (SBO) in patients who have undergone bariatric laparoscopic Roux-en-Y gastric bypass (LGBP) surgery., Materials and Methods: Prospectively entered data from a surgical database of 835 consecutive patients who underwent antecolic-antegastric LGBP for morbid obesity from June 1999 to April 2005 in a single institution were retrospectively reviewed. A total of 42 cases of bowel obstruction were observed in 41 patients. Surgical proof was available in 38 cases, and 4 cases had characteristic imaging features and/or clinical follow-up. Seventeen CT scans were reviewed to determine cause and level of obstruction, and this was correlated with surgical findings and clinical follow-up., Results: Internal hernia was the most common (13 cases) and also the most frequently missed etiology of SBO on CT scans, with the diagnosis being made prospectively in only 2 of 6 cases, in which CT was done. Adhesions, ventral hernia, postoperative ileus, and jejunojejunal (JJ) anastomotic strictures, in that order, were the other commonly observed etiologies for SBO, with 11, 7, 5, and 4 cases, respectively. Some causes of SBO post-LGBP (JJ anastomotic stricture and postoperative ileus) developed relatively early, whereas others (internal hernia) tended to develop later or had a bimodal distribution (adhesions and ventral hernia). Fifteen (36%) of 42 cases had SBO at or near the level of jejunojejunostomy site; causes included internal hernia (5 cases), adhesions/kinking of small bowel (5 cases), JJ anastomotic stricture (4 cases), and JJ intussusception (1 case)., Conclusion: The time interval between LGBP and development of SBO might provide a useful clinical clue to its etiology. The JJ level is an important location for SBO post-LGBP because of a variety of causes, and special attention must be paid to this site at imaging of post-LGBP patients.

Use of laparoscopy in penetrating trauma has been well established; however, its application in blunt trauma is evolving. The authors hypothesized that laparoscopy is safe and feasible as a diagnostic and therapeutic modality in both the patients with penetrating and blunt trauma. Trauma registry data and medical records of consecutive patients who underwent laparoscopy for abdominal trauma were reviewed. Over a 4-year period, 43 patients (18 blunt trauma / 25 penetrating trauma) underwent a diagnostic laparoscopy. Conversion to laparotomy occurred in 9 (50%) blunt trauma and 9 (36%) penetrating trauma patients. Diagnostic laparoscopy was negative in 33% of blunt trauma and 52% of penetrating trauma patients. Sensitivity/specificity of laparoscopy in patients with blunt and penetrating trauma was 92%/100% and 90%/100%, respectively. Overall, laparotomy was avoided in 25 (58%) patients. Use of laparoscopy in selected patients with blunt and penetrating abdominal trauma is safe, minimizes nontherapeutic laparotomies, and allows for minimal invasive management of selected intra-abdominal injuries.