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Additional info for Anti-obesity drug discovery and development Volume 1

Example text

In fact, CMR and CMS are not different concepts, but complementary. While CMR defines a non-quantifiable clinical risk, unlike the classical cardiovascular risk scores, CMS is a pathophysiological concept, and thus it is a pivotal notion in this chapter. The differential key: if we include biomarkers of inflammation, oxidative stress, endothelial dysfunction and prothrombotic state, we should rather refer to CMS, otherwise CMR. Overweight & Obesity LDL-c ApoB HDL-c TG IR Gender Cardiometabolic Syndrome Age Family History Hypercoagulation Genetics Inflammation Hypertension Smoking, Physical Inactivity Figure 10: Cardiometabolic Syndrome.

THE “VASCULO-METABOLIC” THEORY (VMT) This fascinating theory consists of two main pathogenic arms. On one hand, the Vascular Triad includes endothelial dysfunction, oxidative stress and vascular inflammation. On the other, the Metabolic Triad is composed by IR, MI and ER stress. The anatomical substrate remains the same as in the conventional paradigm, namely low-grade fat inflammation and activation of adipose tissue stroma, but according to this new theory, it is interpreted in a bidirectional way, what constitutes its added value (Fig.

These receptors are usually located in the areas responsible for modulating energy balance, feeding behaviour, hepatic lipogenesis, and glucose homeostasis [285]. Endocannabinoid system stimulation promotes metabolic processes that lead to weight gain, lipogenesis, insulin resistance, dyslipidemia, and impaired glucose tolerance [286, 287]. Rimonabant, a CB-1endocannabinoid receptor inhibitor, showed not only to reduce excess body weight in obese subjects, but also a range of both central and metabolic peripheral effects [288], including decreased blood pressure in hypertensive patients, improved insulin sensitivity and dyslipidemia, also decreasing the prevalence of metabolic syndrome [289].

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