Gerhard Prager

Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels.

Background: Different changes of plasma ghrelin levels have been reported following gastric banding, Roux-en-Y gastric bypass, and biliopancreatic diversion. Methods: This prospective study compares plasma ghrelin levels and weight loss following laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) in 20 patients. Results: Patients who underwent LSG (n=10) showed a significant decrease of plasma ghrelin at day 1 compared to preoperative values (35.8 ± 12.3 fmol/ml vs 109.6 ± 32.6 fmol/ml, P=0.005). Plasma ghrelin remained low and stable at 1 and 6 months postoperatively. In contrast, no change of plasma ghrelin at day 1 (71.8 ± 35.3 fmol/ml vs 73.7 ± 24.8 fmol/ml, P=0.441) was found in patients after LAGB (n=10). Increased plasma ghrelin levels compared with the preoperative levels at 1 (101.9 ± 30.3 fmol/ml vs 73.7 ± 24.8 fmol/ml, P=0.028) and 6 months (104.9 ± 51.1 fmol/ml vs 73.7 ± 24.8 fmol/ml, P=0.012) after surgery were observed. Mean excess weight loss was higher in the LSG group at 1 (30 ± 13% vs 17 ± 7%, P=0.005) and 6 months (61 ± 16% vs 29 ± 11%, P=0.001) compared with the LAGB group. Conclusions: As a consequence of resection of the gastric fundus, the predominant area of human ghrelin production, ghrelin is significantly reduced after LSG but not after LAGB. This reduction remains stable at follow-up 6 months postoperatively, which may contribute to the superior weight loss when compared with LAGB.

Drosophila Genome-wide Obesity Screen Reveals Hedgehog as a Determinant of Brown versus White Adipose Cell Fate

Over 1 billion people are estimated to be overweight, placing them at risk for diabetes, cardiovascular disease, and cancer. We performed a systems-level genetic dissection of adiposity regulation using genome-wide RNAi screening in adult Drosophila. As a follow-up, the resulting approximately 500 candidate obesity genes were functionally classified using muscle-, oenocyte-, fat-body-, and neuronal-specific knockdown in vivo and revealed hedgehog signaling as the top-scoring fat-body-specific pathway. To extrapolate these findings into mammals, we generated fat-specific hedgehog-activation mutant mice. Intriguingly, these mice displayed near total loss of white, but not brown, fat compartments. Mechanistically, activation of hedgehog signaling irreversibly blocked differentiation of white adipocytes through direct, coordinate modulation of early adipogenic factors. These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals.

Does Gastric Dilatation Limit the Success of Sleeve Gastrectomy as a Sole Operation for Morbid Obesity

Background: Sleeve gastrectomy as the sole bariatric operation has been reported for high-risk super-obese patients or as first-step followed by Roux-en-Y gastric bypass (RYGBP) or duodenal switch (DS) in super-super obese patients. The efficacy of laparoscopic sleeve gastrectomy (LSG) for morbidly obese patients with a BMI of <50 kg/m2 and the incidence of gastric dilatation following LSG have not yet been investigated. Methods: 23 patients (15 morbidly obese, 8 super-obese) were studied prospectively for weight loss following LSG. The incidence of sleeve dilatation was assessed by upper GI contrast studies in patients with a follow-up of >12 months. Results: Patients who underwent LSG achieved a mean excess weight loss (EWL) at 6 and 12 months postoperatively of 46% and 56%, respectively. No significant differences were observed in %EWL comparing obese and super-obese patients. At a mean follow-up of 20 months, dilatation of the gastric sleeve was found in 1 patient and weight regain after initial successful weight loss in 3 of the 23 patients. Conclusion: LSG has been highly effective for weight reduction for morbid obesity even as the sole bariatric operation. Gastric dilatation was found in only 1 patient in this short-term follow-up. Weight regain following LSG may require conversion to RYGBP or DS. Follow-up will be necessary to evaluate long-term results.

CC Chemokine and CC Chemokine Receptor Profiles in Visceral and Subcutaneous Adipose Tissue Are Altered in Human Obesity

BACKGROUND/AIMS Obesity is associated with a low-grade inflammation, insulin resistance, and macrophage infiltration of adipose tissue. The role of CC chemokines and their respective receptors in human adipose tissue inflammation remains to be determined. METHODS sc and visceral adipose tissue of obese patients (body mass index 53.1 +/- 11.3 kg/m(2)) compared with lean controls (body mass index 25.9 +/- 3.8 kg/m(2)) was analyzed for alterations in inflammatory gene expression. RESULTS Macrophage infiltration was increased in sc and visceral adipose tissue of obese patients as determined by increased mRNA expression of a macrophage-specific marker (CD68) and by elevated macrophage infiltration. Gene expression of CC chemokines involved in monocyte chemotaxis (CCL2, CCL3, CCL5, CCL7, CCL8, and CCL11) and their receptors (CCR1, CCR2, CCR3, and CCR5) was higher in sc and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker IL-6 and C-reactive protein were elevated in obese patients compared with lean controls. Obese patients revealed increased insulin resistance as assessed by the homeostasis model assessment of insulin resistance index and reduced plasma adiponectin concentrations. Adipose tissue expression of many CC chemokines and their receptors in the obese group positively correlated with CD68 expression. CONCLUSION Up-regulation of the CC chemokines and their respective receptors in adipose tissue occurs in human obesity and is associated with increased systemic inflammation.

Long-chain n−3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial

BACKGROUND Chronic adipose tissue inflammation is a hallmark of obesity, triggering the development of associated pathologies, particularly type 2 diabetes. Long-chain n-3 PUFAs reduce cardiovascular events and exert well-established antiinflammatory effects, but their effects on human adipose tissue inflammation are unknown. OBJECTIVE We investigated whether n-3 PUFAs reduce adipose tissue inflammation in severely obese nondiabetic patients. DESIGN We treated 55 severely obese nondiabetic patients, scheduled to undergo elective bariatric surgery, with 3.36 g long-chain n-3 PUFAs/d (EPA, DHA) or an equivalent amount of butterfat as control, for 8 wk, in a randomized open-label controlled clinical trial. The primary efficacy measure was inflammatory gene expression in visceral and subcutaneous adipose tissue samples (subcutaneous adipose tissue and visceral adipose tissue), collected during surgery after the intervention. Secondary efficacy variables were adipose tissue production of antiinflammatory n-3 PUFA-derived eicosanoids, plasma concentrations of inflammatory markers, metabolic control, and the effect of the Pro12Ala PPARG polymorphism on the treatment response. RESULTS Treatment with n-3 PUFAs, which was well tolerated, decreased the gene expression of most analyzed inflammatory genes in subcutaneous adipose tissue (P < 0.05) and increased production of antiinflammatory eicosanoids in visceral adipose tissue and subcutaneous adipose tissue (P < 0.05). In comparison with control subjects who received butterfat, circulating interleukin-6 and triglyceride concentrations decreased significantly in the n-3 PUFA group (P = 0.04 and P = 0.03, respectively). The Pro12Ala polymorphism affected the serum cholesterol response to n-3 PUFA treatment. CONCLUSIONS Treatment with long-chain n-3 PUFAs favorably modulated adipose tissue and systemic inflammation in severely obese nondiabetic patients and improved lipid metabolism. These effects may be beneficial in the long-term treatment of obesity. This trial was registered at clinicaltrials.gov as NCT00760760.

After massive weight loss: patients' expectations of body contouring surgery.

BackgroundMassive weight loss following bariatric surgery leads to excess skin with functional and aesthetic impairments. Surplus skin can then contribute to problems with additional weight loss or gain. The aims of the current study were to evaluate the frequency of massive soft tissue development in gastric bypass patients, to determine whether males and females experience similar post-bypass body changes, and to learn about the expectations and impairments related to body contouring surgery.MethodsA questionnaire addressing information on the satisfaction of body image, quality of life, and expectation of body contouring surgery following massive weight loss was mailed to 425 patients who had undergone gastric bypass surgery between 2003 and 2009. Of these 425 individuals, 252 (59%) patients completed the survey.ResultsNinety percent of women and 88% of men surveyed rated their appearance following massive weight loss as satisfactory, good, or very good. However, 96% of all patients developed surplus skin, which caused intertriginous dermatitis and itching. In addition, patients reported problems with physical activity (playing sports) and finding clothing that fit appropriately. Moreover, 75% of female and 68% of male patients reported desiring body contouring surgery. The most important expectation of body contouring surgery was improved appearance, followed by improved self-confidence and quality of life.ConclusionsSurplus skin resulting from gastric bypass surgery is a common issue that causes functional and aesthetic impairments in patients. Consequently, this increases the desire for body contouring surgery with high expectations for the aesthetic outcome as well as improved life satisfaction.

Tissue oxygenation in obese and non-obese patients during laparoscopy

Background: Wound infection risk is inversely related to subcutaneous tissue oxygenation, which is reduced in obese patients and may be reduced even more during laparoscopic procedures. Methods: We evaluated subcutaneous tissue oxygenation (PsqO2) in 20 patients with a body mass index (BMI) ≥40 kg/m2 (obese group) and 15 patients with BMI <30 kg/m2 (non-obese group) undergoing laparoscopic surgery with standardized anaesthesia technique and fluid administration. Arterial oxygen tension was maintained near 150 mmHg. PsqO2 was measured from a surrogate wound on the upper arm. Results: A mean FIO2 of 51% (13%) was required in obese patients to reach an arterial oxygen tension of 150 mmHg; however, a mean FIO2 of only 40% (7%) was required to reach the same oxygen tension in non-obese patients (P=0.007). PsqO2 was significantly less in obese patients: 41 (10) vs 57 (15) mmHg (P<0.001). Conclusion: Obese patients having laparoscopic surgery require a significantly greater FIO2 to reach an arterial oxygen tension of about 150 mmHg than non-obese patients; they also have significantly lower subcutaneous oxygen tensions. Both factors probably contribute to an increased infection risk in obese patients.

The Prevalence of Body Contouring Surgery After Gastric Bypass Surgery

BackgroundAs bariatric surgery has become more popular, more patients are undergoing body contouring surgery after massive weight loss. Many of the surgical procedures performed on the massive weight loss patient are complex and labor-intensive. Therefore, the plastic surgery unit needs to be prepared for a patients demand. Little literature is available on how frequently patients who have undergone gastric bypass surgery receive body contouring surgery.MethodsTwo hundred fifty-two subjects (out of 425 who were mailed the questionnaire) who had undergone gastric bypass surgery between 2003 and 2009 completed the questionnaire, which obtained information on body image satisfaction and frequency of body contouring surgery after massive weight loss.ResultsOf all patients, 74% desire a body contouring surgery after gastric bypass surgery. Fifty-three patients (21%) have undergone a total of 61 body contouring procedures. The most common were abdominoplasties (59%), followed by lower body lifts (20%). In contrast to a positive judgment of the general aspect of the body image satisfaction after massive weight loss, both genders are unsatisfied with body areas like abdomen/waist, breast, and thighs.ConclusionsParalleling the increasing use of bariatric surgery, there is a high demand for body contouring surgery. A huge disparity exists between the number of subjects who desire a body contouring surgery and those who actually received it.

Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients.

Accumulation of cytotoxic and T‐helper (Th)1 cells together with a loss of regulatory T cells in gonadal adipose tissue was recently shown to contribute to obesity‐induced adipose tissue inflammation and insulin resistance in mice. Human data on T‐cell populations in obese adipose tissue and their potential functional relevance are very limited. We aimed to investigate abundance and proportion of T‐lymphocyte sub‐populations in human adipose tissue in obesity and potential correlations with anthropometric data, insulin resistance, and systemic and adipose tissue inflammation. Therefore, we analyzed expression of marker genes specific for pan‐T cells and T‐cell subsets in visceral and subcutaneous adipose tissue from highly obese patients (BMI >40 kg/m2, n = 20) and lean to overweight control subjects matched for age and sex (BMI <30 kg/m2; n = 20). All T‐cell markers were significantly upregulated in obese adipose tissue and correlated with adipose tissue inflammation. Proportions of cytotoxic T cells and Th1 cells were unchanged, whereas those of regulatory T cells and Th2 were increased in visceral adipose tissue from obese compared to control subjects. Systemic and adipose tissue inflammation positively correlated with the visceral adipose abundance of cytotoxic T cells and Th1 cells but also regulatory T cells within the obese group. Therefore, this study confirms a potential role of T cells in human obesity‐driven inflammation but does not support a loss of protective regulatory T cells to contribute to adipose tissue inflammation in obese patients as suggested by recent animal studies.

One-Year Experience with Tantalus™: a New Surgical Approach to Treat Morbid Obesity

Background: Increased caloric density in modern processed foods may be an important factor underlying the prevalence of obesity, because low-volume, high-caloric food intake may delay activation of volume-dependent gastric mechanical activity known to induce the feeling of fullness. We therefore hypothesized that enhancement of gastric contractions by electrical stimulation at an early stage of the meal will reduce food intake and body weight in morbidly obese subjects. Methods: The study was a prospective, non-randomized, open-label, single-center trial. 12 subjects (age 36.1 ± 2.8 years, BMI 43.2 ± 2.7 kg/m2, weight 128.8 ± 5.2 kg, means±SEM) underwent laparoscopic implantation with the Tantalus™ system. A pulse generator with 3 bipolar leads was implanted: 2 pairs in the antrum and a 3rd pair in the fundus. The system was activated at week 6. All subjects were followed for 20 weeks and 9 of them for 52 weeks. Results: All subjects finished the initial 20-week observation period. Following activation of the Tantalus™ System, a reduction (P<0.05) in hunger and an increase in cognitive control (P<0.05) as assessed by the Three-Factor Eating Questionnaire (TFEQ) could be observed. Body weight decreased (P<0.05) from 128.8±5.2 to 119.9+5.9 (17.6+4.3% EWL, N=12) after 20 weeks (14 weeks of treatment). In the 9 subjects continuing for 52 weeks (46 weeks of treatment), body weight further decreased to 112.4 ± 3.8 kg (26.6 ± 8.5 %EWL, N=9). Blood pressure decreased (P<0.05) from 142 ± 6.1/91 ± 3.2 to 125.5 ± 4.0/83 ± 2.6 mmHg by week 20 and 128.8 ± 3.8 / 86.3 ± 3.6 mmHg after 1 year. The frequency and severity of device and/or procedure-related adverse events indicate that the method is safe and well-tolerated. Conclusion: This data suggests that gastric stimulation by the minimally invasive Tantalus™ System is safe and leads to favorable changes in eating behavior, clinically significant weight loss and reduction in blood pressure. Treatment with the Tantalus™ System is therefore a promising minimally invasive treatment for obesity.