Studies On The Anti-Obesity Effects Of Betaphrine In Obese Animal Induced By Monosodium-L-Glutamate

Background and purposeThe morbidity and mortality of obesity is increasing as many countries develop all over the world. The WHO has confirmed obesity is the most common chronic disease in adults. It is considered to be one of four medicosocial problems in the world. Preservation and treatment of obesity has become the most important health problem in the 21st century. At present, the most important treatment method of obesity is drug treatment. Sibutramine and Orlistat ratified by the FDA have cardiovascular side effects. Nowadays, there isn't a secure and effective agent to treat the obesity. So to find a high selective weight-reducing target has become a hot spot.Many studies have indicated thatβ3 adrenoceptor (β3-AR)agonist can reduce blood glucose , serum lipid and body weight by stimulating lipolysis of white adipose tissue(WAT) and nonshivering thermogenesis( NST) of brown adipose tissue(BAT). Animal experiments indicated that Betaphrine(Bet)can obviously reduce body weight. It may be a selectiveβ3-AR agonist. But someβ3-AR agonist effective in animal model have no obvious effect in human, which may be caused byβ3-AR species differences, different selectivity, bioavailability and half-life of drug, et al. Up to now, researchers all over the world haven't found an high selective and effectiveβ3-AR agonist to treat the obesity in human being.Methods:We observed acute toxic action of Bet in mice by Bliss, and determine lethal dose50 and maximally tolerated dose, which provided evidence for animal pharmacodynamics. We determined index in obese rats induced by MSG, including body weight, Lee's indexes, WAT , BAT, adipose coefficient , the number and size of adipocytes, total cholesterol(TC), triglyeride(TG), low-density lipoprotein(LDL), high-density lipoprotein(HDL), free fatty acid(FFA), glucose(Glu), insulin(INS), neuropeptide(NPY), Leptin(LEP) in plasma and hypothalamus to explore the antiobesity action of Bet in obese rats induced by MSG.Results:1. Observation results of acute toxicity testing of Bet in mice, the demonstrable LD50 of Bet is shown as 893.61mg/kg by intragastric administration and 195.58mg/kg by intravenous injection in mice.2. Obese rat models were successfully induced by MSG.3.Bet could significantly reduce body weight, adipose tissue ,adipose coefficient , size of adipocytes, serum Glu, TC, TG and INS in plsma and hypothalamus and increase number of adipocytes and serum HDL. We found that it had no significant effect on NPY and LEP.Concludingly, the present study indicated that Bet had significant antiobesity action. The effects of Bet(90mg/kg) were equal to the action of Sib(4mg/kg).The mechanisms of Bet may be including(1)Promoting energy metabolism in obese rats.(2) Accelerating lipolysis.(3)Reducing serum TC and TG and increasing serum HDL level,which had positive prevention on cardiovascular complication in obese rats.(4)Reducing serum INS and improving insulin resistance and hyperinsulinemia.