Rapid and body weight-independent improvement of endothelial and high-density lipoprotein function after Roux-en-Y gastric bypass: role of glucagon-like peptide-1.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) reduces body weight and cardiovascular mortality in morbidly obese patients. Glucagon-like peptide-1 (GLP-1) seems to mediate the metabolic benefits of RYGB partly in a weight loss-independent manner. The present study investigated in rats and patients whether obesity-induced endothelial and high-density lipoprotein (HDL) dysfunction is rapidly improved after RYGB via a GLP-1-dependent mechanism. METHODS AND RESULTS: Eight days after RYGB in diet-induced obese rats, higher plasma levels of bile acids and GLP-1 were associated with improved endothelium-dependent relaxation compared with sham-operated controls fed ad libitum and sham-operated rats that were weight matched to those undergoing RYGB. Compared with the sham-operated rats, RYGB improved nitric oxide (NO) bioavailability resulting from higher endothelial Akt/NO synthase activation, reduced c-Jun amino terminal kinase phosphorylation, and decreased oxidative stress. The protective effects of RYGB were prevented by the GLP-1 receptor antagonist exendin9-39 (10 µg·kg(-1)·h(-1)). Furthermore, in patients and rats, RYGB rapidly reversed HDL dysfunction and restored the endothelium-protective properties of the lipoprotein, including endothelial NO synthase activation, NO production, and anti-inflammatory, antiapoptotic, and antioxidant effects. Finally, RYGB restored HDL-mediated cholesterol efflux capacity. To demonstrate the role of increased GLP-1 signaling, sham-operated control rats were treated for 8 days with the GLP-1 analog liraglutide (0.2 mg/kg twice daily), which restored NO bioavailability and improved endothelium-dependent relaxations and HDL endothelium-protective properties, mimicking the effects of RYGB. CONCLUSIONS: RYGB rapidly reverses obesity-induced endothelial dysfunction and restores the endothelium-protective properties of HDL via a GLP-1-mediated mechanism. The present translational findings in rats and patients unmask novel, weight-independent mechanisms of cardiovascular protection in morbid obesity.

Operative strategies for patients with failed primary bariatric procedures.

Bariatric surgery is the most effective therapy to treat obesity and its sequelae. With the increasing incidence of obesity, the number of bariatric procedures has dramatically increased in recent years. The perioperative morbidity reached a very low level, and nearly all revisional bariatric procedures are primarily minimally invasive today. About 10-25% of the patients undergoing bariatric surgery require a revision at some point after their initial operation. Consequently, revisional bariatric surgery has emerged as a distinct practice, performed mainly at tertiary centers, to resolve complications caused by the primary operation and to provide satisfactory weight loss. In this review, our personal experience with revisional bariatric surgery is discussed against the background of the available literature. We further attempt to define major indications for revisional bariatric surgery and balance them with perioperative and long-term morbidity as well as the surgical outcome.

[Update on fecal incontinence]. / Stuhlinkontinenz - ein Update.

Fecal incontinence is defined as an accidental loss of stool or the inability to control defecation. There are three subtypes of fecal incontinence: passive incontinence, urge incontinence and soiling. About 8% of the adult population suffer from fecal incontinence, but only 1/3 consults a doctor. Beside the individual handicap, fecal incontinence has a huge socio-economic impact. Causes of fecal incontinence are changes in the quantity or quality of the stool and structural or functional disorders. Diagnostics encompass the medical history, clinical examination including the digital rectal examination, imaging (particularly endoanal ultrasound) as well as functional diagnostics (anal manometry and defecography). Nowadays, the most promising conservative treatment option consists of loperamide and biofeedback therapy. The most successful invasive method is the sacral neuromodulation.

L'incontinence fécale est définie comme une perte accidentelle de selles ou l'incapacité de contrôler la défécation. Il y a trois types d'incontinence fécale: l'incontinence passive, le besoin irrépressible et les salissures. Approximativement 8% de la population adulte souffre d'incontinence fécale, mais seulement 1/3 d'entre eux consultent un médecin. En plus de l'handicap individuel, l'incontinence fécale a un impact socio-économique considérable. Les causes de l'incontinence fécale comportent des modifications de la quantité ou de la qualité des selles et des anomalies structurelles ou fonctionnnelles. L'approche diagnostique comporte l'anamnèse médicale, l'examen clinique incluant un toucher rectal, le recours à l'imagerie (en particulier l'ultrasonographie endoanale) et des examens fonctionnels comme la manométrie anale et la défécographie. Aujourd'hui le traitement conservateur le plus prometteur se base sur le loperamide et la thérapie par biofeedback. La méthode invasive la plus efficace est la neuromodulation sacrée.

The gut-brain axis in obesity.

Currently the only effective treatment for morbid obesity with a proven mortality benefit is surgical intervention. The underlying mechanisms of these surgical techniques are unclear, but alterations in circulating gut hormone levels have been demonstrated to be at least one contributing factor. Gut hormones seem to communicate information from the gastrointestinal tract to the regulatory appetite centres within the central nervous system (CNS) via the so-called 'Gut-Brain-Axis'. Such information may be transferred to the CNS either via vagal or non-vagal afferent nerve signalling or directly via blood circulation. Complex neural networks, distributed throughout the forebrain and brainstem, are in control of feeding and energy homoeostasis. This article aims to review how appetite is potentially regulated by these gastrointestinal hormones. Identification of the underlying mechanisms of appetite and weight control may pave the way to develop better surgical techniques and new therapies in the future.