**3. Antiobesity and lipid lowering effects**

The various experimental studies reported decrease in serum TC, TG and LDL-C concentrations and an increase in serum high density lipoprotein-cholesterol (HDL-C) for bitter melon by different authors. The action of bitter melon in lowering fat has been supported by plentiful studies, its effect on the level of serum FFAs have been contradictory with some authors showing reduction, some shown same level, and others reported an increased levels. For example, the serum FFAs concentration increased in obese rats treated with bitter melon shown by Chen et al. [21]. An increased level of TG and LDL-C in the serum that may arises due to either overproduction by the liver or defective removal from the circulation or the overall dyslipidaemia in diabetes. It is not clear why bitter melon increase the serum level of FFAs. It may facilitate fat mobilization due to the suppression of lipogenesis or lipid deposition. While other revealed *M. charantia* L. could lower the serum and liver TG levels [22].

The findings of experimental research conclude that, *M. charantia* L. may reduce the fasting insulin, TG, cholesterol and epididymal fat, which were increased by HFD. The dwindling of insulin resistance, improves glucose tolerance, and increases insulin signaling under HFD-induced insulin-resistance and elevated serum lipids may also shown by bitter melon. The administration of an aqueous extract of unripe fruits of bitter melon improved glucose and insulin tolerance together with inhibition of plasma apoB-100 and apoB-48. The animal study had shown that, the evidence of a potent inhibitor of apoB secretion and TG synthesis as well as the plasma lipid and VLDL effects of bitter melon juice [23]. Overall the studies on the fruits, seeds, and aerial parts of *M. charantia* Linn have been shown to reduce adiposity, lower serum insulin and normalize glucose tolerance in rats fed with a HFD. The body weight and visceral fat mass of bitter melon treated obese rats were shown to be lowered [24].

While further study revealed that, bitter melon supplementation into HFD notably suppressed the levels of fatty acid synthase (FAS), acetyl-CoA carboxylase-1 (ACC-1), lipoprotein lipase (LPL) and adipocyte fatty acid binding protein [25]. Water extract of *M. charantia* L. fruits at a dose 1 g/Kg body weight revealed to be effectual in improving the obesity-induced hyperglycaemia and hyperleptinemia [26]. This in progression propose that bitter melon can reduce insulin resistance, visceral fat accumulation and adipocyte hypertrophy probably by down-regulating the expression of key lipogenic genes or proteins in adipose tissues. Aqueous fruit extract of *M. charantia* L. significantly reduce the level of serum TG, TC, LDL and VLDL at a dose of 350 mg/Kg body weight in experimental rats [27]. Numerous

animal studies have been designated the efficacy of bitter melon in the amelioration of weight gain and regulation of lipid metabolism [28].

The methanolic extract of fruit of bitter melon showed antidiabetic and antihyperlipidemic action during different seasons of the year, this suggests that antidiabetic and hypolipidemic activity of *M. charantia* L. may fluctuate on quantity and quality of active constituents during different seasons of the year and reach the peak during spring [29]. The bitter melon seed oil had shown significantly decreased in body-weight, Lee's index, fat index and adipose size in the HFD mice. Meanwhile, the serum FFAs levels returned to normal at the dosage of 10 g/kg [30]. *Momordica charantia* L. extracts have anti-obesity effects and the ability to modulate lipid prolife of mice fed a HFD by suppressing body weight gain, visceral tissue weight, plasma and hepatic lipid concentrations, and lipid peroxidation along with increasing lipid metabolism. The plasma TG, TC, and LDL-C levels along with hepatic TG and TC concentrations considerably lowered in mice fed a HFD by *Momordica charantia* L. extracts. Also elevated plasma HDL-C levels and fecal TG concentration shown in animals treated with the extracts. The extracts comprise anti-obesity effects in mice fed a HFD by inhibiting lipid peroxidation whereas increasing lipid metabolism [31]. Bitter melon extract showed useful benefit on body weight gain and fat deposition.

Moreover, bitter melon reduced the lipid accumulation during differentiation from a pre-adipocyte to adipocyte and down-regulated PPAR [32]. PPAR is considered the master regulator of adipogenesis during differentiation of pre-adipocyte to adipocyte [33]. Bitter melon juice inhibited adipocyte differentiation by reducing PPAR, SREBP, and perilipin mRNA gene expression and by increasing lipolysis in primary human adipocyte [34]. Several transcriptional regulatory factors like AMPK, PPAR, and PGC-1 regulate the mitochondrial biogenesis, which would be a possible way of increasing lipid metabolism and utilization in energy demanding cells and tissues [35]. PGC-1 stimulates mitochondrial biogenesis and respiration in multiple cell types and modulates biological programs normally associated with increased oxidative metabolism. Also decreased plasma level of TGs, cholesterol, and FFA in plasma of rats fed a HF diet revealed by bitter melon supplementation due to up regulation and activation of PGC-1 [36].

Bitter melon affects on various body organs to treat obesity and diabetes as [37]:

#### 1.Liver


#### 2.Pancreas

