肥胖相關代謝症候群與減肥藥

Obesity Related Metabolic Complications and Antiobesity Drugs

肥胖及體重過高會引起高血壓、第二型糖尿病、血管硬化、癌及其他代謝症候群。抑制食慾或降低對營養吸收是防止肥胖相關代謝症候群的首要。已知有超過40 種以上內分泌、神經肽、酶、細胞信息傳遞分子、及其作用的受體參與體重的調控。而從脂肪細胞及滲透到脂肪組織的巨噬細胞所分泌的瘦體素、脂連素、色素上皮細胞衍生因子、胰島素抗藥素、發炎體及其他發炎性脂肪細胞素都與代謝症候群相關。這樣複雜的關係及不同因素間的回饋作用使得開發處理肥胖新藥不易成功，但是它們仍是開發減肥藥之作用標的。Accomplia 是大麻受體 (CB1 ) 抑制劑，Sibutramine 是單胺回收抑制劑，由於產生嚴重毒性而自減肥藥市場下架，促使藥廠開發二種作用機理不同藥物合一的新配方，以降低藥物毒性。如Orexigen 藥廠的Contrave (bupropion 加naltrexone ) 及Empatic (bupropion 加zonisamide )， 與Vivus 藥廠的Qnexa (phentermine 加topiramate)。以上顯示，透過多重藥物標的以預防或處理代謝症候群這樣多因素引起的疾病，是很重要的原則。緘默信息調整蛋白質，被認為是處理老年病之標的，而從葡萄得到的白藜蘆醇，在高濃度或高劑量可活化緘默信息調節蛋白質，它也有其他作用機理，而比它作用更強的物質也被報導過。除了這些，不少植物藥及中藥被報導將是有用的能量攝取或食慾抑制劑。

Obesity and overweight caused hypertension, type 2 diabetes, atherosclerosis, cancer and other metabolic complications (M.C.). Therefore, control of body weight by inhibiting appetite or nutrient absorption is essential for the prevention of M.C. More than 40 hormones, neuropeptides, enzymes, cell signaling molecules and their receptors are involved in the regulation of body weight. Being related to M.C., leptin, adiponectin, pigment epithelium derived factor, resistin, inflammasomes, and other inflammatory adipocytokines released from adipocytes and macrophage that infiltrated to adipose tissue. Such a complexity and reciprocal feedback mechanisms make the development of new anti-obesity drugs to be with minimal success. Still, they are targets for future anti-obesity drugs. Accomplia and Sibutramine suppress appetite by acting on cannabinoid (CB1) receptor and inhibiting monoamine reuptake, respectively. They were withdrawn from the market for their serious toxic effects, which leads to the approach by combining two drugs to decrease their toxicity. Those are Contrave (bupropion+naltrexone), Empatic (bupropion+zonisamide) from Orexigen, and Qnexa (phentermine+topiramate) from Vivus. These demonstrated that multiple drug treatment is an important principle for the prevention or management of multiple factorial diseases such as M.C. Sirutins are therapeutic target to treat age-associated diseases. Resveratrol from grape is a sirutins activator and also has other mechanisms in high concentrations or doses. Other compounds acting as more potent sirutins activators have been reported. Moreover, many herbal medicines including traditional Chinese medicine could be useful for the suppression of energy intake or appetite.