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Obesity is a chronic disease characterized by an accumulation of excess adipose tissue and associated with an increased risk of multiple morbidities and mortality. Unfortunately, once adipose tissue accumulates, a system of overlapping neuroendocrine responses prevents it from diminishing. Pharmacological intervention is often necessary to aid in inducing weight loss and maintenance.

Obesity is rapidly growing in the US and worldwide. Recent reports estimate that 66% of US adults are overweight (33%) or obese (33%) and that 17% of US children are overweight. This rapid growth in the incidence of obesity is seen worldwide, albeit somewhat delayed and in some cases at a slower rate. It is estimated that medical expenses in 1998 associated with both overweight and obesity accounted for 9.1 percent of total U.S. medical expenditures. Given the continuing increase in the incidence of overweight and obesity, it is estimated that these costs have risen further.

The Simbiosys obesity discovery platform consists of assaying solutions for a portfolio of clinically validated as well as emerging therapeutic targets.

Cannabinoid receptor type 1 (CB1)
 

CB1 and associated endogenous ligands, the endocannabinoids, participate in the central regulation of food intake. Endogenous cannabinoids, through stimulation of CB1 receptors, stimulate hunger and promote appetite and are increased during fasting and reduced after feeding. Importantly, at peripheral level CB1 activation has been shown to stimulate lipogenesis into adipocytes, and CB1 antagonists have been found to be important positive modulators of adiponectin secretion. Therefore, the endocannabinoid system is an important modulator of a plethora of effects largely impacting food intake control and metabolic processes.

Pancreatic Lipase
 

Pancreatic lipase is the main enzyme responsible for breaking down fats in the human digestive system. It is a lipase which converts triglyceride substrates found in oils from food to monoglycerides and free fatty acids. Pancreatic lipase has recently received attention as a target for management of obesity. Clinical trials support the contention that inhibiting lipase can lead to significant reductions in body weight in some patients. The drug orlistat (Xenical) is a pancreatic lipase inhibitor that interferes with digestion of triglyceride and thereby reduces absorption of dietary fat.

5-HT2c Serotonin Receptor
 

Brain serotonin levels are thought to play an important role in the neural regulation of appetite. 5-HT2c serotonin receptor deficient mice have been shown to increase body weight and fat depot weight entirely because of increased food intake, suggesting that postsynaptic 5-HT2c serotonin receptors confer the anorectic effect of serotonin.

 

 
Assay Development
Cell Isolation & Banking
Cell Line Development
Natural Product Testing
Molecular Biology
Bioinfomatics

 

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