Undurti N. Das

A surgical rat model of human Roux-en-Y gastric bypass

Obesity affects 30% of the United States population and its detrimental effects are obesity-related metabolic diseases. For patients refractory to conventional weight loss therapy, gastric bypass surgery is one of the proven methods for inducing a sustained weight loss and reversing the metabolic sequelae of obesity. To understand the mechanisms of weight loss and the amelioration of related metabolic comorbid conditions, a reproducible animal model is needed. We report our developmental experience with rat models of sequential Roux-en-Y gastric bypass after reproducing the diet-induced obesity that characterizes the hallmarks of human obesity. Four experiments were performed to induce weight reduction through successive modifications: In Experiment 1 a 20% stapled gastric pouch with a 16 cm biliarypancreatic limb and a 10 cm alimentary limb accomplished sufficient weight loss within 10 days to ameliorate metabolic changes associated with obesity, but the occurrence of gastrogastric fistulas prevented sustained weight loss; in Experiment 2 the model was improved by dividing the stomach to avoid gastrogastric fistula, but again sustained weight loss was not achieved; in Experiment 3 the biliarypancreatic limb was lengthened from 16 to 30 cm, reducing the common channel to approximately 18 cm. Sustained weight loss was achieved for 28 days. In Experiment 4 the model in Experiment 3 was modified by dividing the stomach between two rows of staples. Sustained weight loss was observed for 67 days. We developed a reproducible rat model of Roux-en-Y gastric bypass. The existence of this model opens a new field of research in which to study the metabolic sequelae of obesity and the mechanisms of weight loss.

Interleukin-1beta system in anorectic catabolic tumor-bearing rats.

Purpose of reviewThe onset of cancer anorexia and the accompanying neurological symptoms and signs involve the general influence of cytokines on the brain. Using methylcholanthrene to induce tumors in Fischer 344 rats, we measured various specific components of the cytokine-induced anorectic reaction, including: (1) IL-1β system components (ligand, signaling receptor, receptor accessory proteins, and receptor antagonist); (2) TNF-α; (3) TGF-β1; and (4) IFN-γ in the tumor tissue, the liver and the brain. Recent findingsThe data show that IL-1β, TNF-α and IFN-γ messenger RNA were detected in the tumor tissue of anorectic tumor-bearing rats. In brain regions, anorexia is associated with the upregulation of IL-1β and its receptor mRNA. All other mRNA remained unchanged in the brain regions examined. SummaryThis suggests that IL-1β and its receptor may play a significant role in this model of cancer-associated anorexia. In vivo, the characterization of cytokine components in the brain may provide data for potential pharmacological interventions to ameliorate the anorexia of disease.

Tumor anorexia: effects on neuropeptide Y and monoamines in paraventricular nucleus

Paraventricular (PVN) concentrations of neuropeptide Y (NPY), serotonin (5-HT) and dopamine (DA) in anorectic tumor-bearing (TB) rats were measured before and after tumor resection. At onset of anorexia in TB versus non-tumor bearing (NTB) Controls 5-HT increased from 12.19+/-0.49 pg/microg to 14.89+/-0.81 pg/microg ( P<0.05 ) while DA and NPY decreased from 7.34+/-0.42 pg/microg to 4.97+/-0.56 pg/microg and 23.47+/-4.27 pg/microg to 13.64+/-1.44 pg/microg, respectively ( P<0.05 ). After tumor resection, these neuromediators normalized when compared to sham-operated NTB rats. NTB pair-fed Controls were also studied. We conclude that the increased 5-HT and the decreased DA and NPY concentrations in PVN are associated with cancer anorexia and that the NPY food stimulatory effect is linked to serotoninergic and dopaminergic systems in hypothalamus.

Metabolic alterations during inflammation and its modulation by central actions of omega-3 fatty acids.

Purpose of review To discuss the possible relationship between long‐chain polyunsaturated fatty acids, cytokines, anandamides, nitric oxide, leptin, various neurotransmitters in the brain, and their role in anorexia of acute and chronic inflammatory conditions and cancer. Recent findings Recent studies have shown that long‐chain polyunsaturated fatty acids, especially the omega‐3 series, have antiinflammatory actions, increase the concentrations of anandamides, enhance the levels of acetylcholine and nitric oxide and modulate the concentrations and actions of various neurotransmitters, including leptin, in the brain. Patients suffering from acute and chronic inflammatory conditions have low tissue concentrations of various long‐chain polyunsaturated fatty acids, and high levels of proinflammatory cytokines that can cause anorexia and decrease food intake. Summary It is suggested that supplementation of long‐chain polyunsaturated fatty acids may have a role in the prevention and treatment of acute and chronic inflammatory conditions, improving anorexia associated with these conditions.