Obesity is a major public health problem in developed countries as well as in developing countries [1
]. The prevalence of obesity is steadily increasing and has more than doubled since 1980. According to World Health Organization (WHO) global estimates from 2008, over 500 million adults are obese (http://www.who.int/mediacentre/factsheets/fs311/en
). Obesity is becoming leading risk for global deaths. At least 2.8 million adults die each year as a result of being overweight or obese. With severe obesity, over 30 kg/m2
body mass index (BMI), mortality is substantially elevated by 50-150% [2
]. In addition, obesity is strongly associated with the development of serious diseases such as type 2 diabetes mellitus, cardiovascular diseases, and certain cancers [3
Obesity has many causes including excessive intake of calories, genetic factors, endocrine dysfunction, metabolic disorders, and stresses [6
]. Among these causes, excessive energy intake is the most common risk factor of obesity. The major dietary fat, triglycerides (TG), provide the major source of energy. TG is transported in the blood as lipoproteins and stored in adipose tissues [7
]. The major classes of blood lipoproteins are chylomicrons, very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoprotein (LDL), and high-density lipoproteins (HDL). Chylomicrons are produced in intestinal cells from dietary lipid, and VLDL is produced in the liver, mainly from dietary carbohydrates. IDL and LDL are produced in blood capillary by digestion of the TG or VLDL. HDL transfers an activator of lipoprotein lipase (LPL) to chylomicrons and VLDL. HDL also carries cholesterol from peripheral tissues to the liver. TG of chylomicrons and VLDL are hydrolyzed by LPL to fatty acid and glycerol. The fatty acids may be oxidized by various tissues. In adipose cells, the fatty acids are converted TG and stored.
To treat obesity, constant control of diet and exercise are required [8
]. However, it is hard for obese patients to maintain regular exercising steadily. Synthetic appetite suppressants or fat absorption blockers have been developed as anti-obesity drugs, yet the efficacy and long-term safety level of the drugs were not fully evaluated [9
]. Therefore, safe and efficient anti-obesity substances are still needed.
Silkworm (Bombyx mori
) has been ingested for a long time in Asian countries. It is well known that silk peptides (SP) and silkworm pupa peptides (SPP) have a blood glucose-regulating effect [11
]. Recently, we demonstrated that SPP suppresses adipogenesis in preadipocytes and fat accumulation in rats [15
]. Notably, in spite of body weight-lowering effect, silk amino acids (SAA) enhanced physical stamina [16
is an edible native Southeastern Asian fruit, used as spices [18
]. Garcinia cambogia
contains hydroxycitric acid (HCA), a competitive inhibitor of adenosine triphosphate (ATP) citrate lyase [18
]. HCA reduces the acetyl-CoA pool, thus limiting the biosynthesis of fatty acid and cholesterol.
White bean (Phaseolus vulgaris
) contains a high level of pancreatic α-amylase inhibitor [21
]. It has been shown that the long-term administration of the α-amylase inhibitor from white bean extract reduced blood glucose levels and body weight gain in rats.
Mango is a rich source of various polyphenolic compounds [23
]. Mango polyphenols, like other polyphenolic compounds, have a great antioxidative potential and they are expected to reduce degenerative diseases such as cancer, atherosclerosis, diabetes, and obesity [23
Raspberry (Rubus idaeus
) contains raspberry ketone, a major aromatic compound of red raspberry [25
]. Raspberry ketone prevents and improves obesity and fatty liver by increasing norepinephrine-induced lipolysis in white adipocytes [25
Cocoa can prevent high-fat diet-induced obesity by modulating lipid metabolism, especially by decreasing fatty acid synthesis and transport systems, and enhancement of a part of the thermogenesis mechanism in the liver and white adipose tissues [28
Green tea contains a series of polyphenols known as catechins [29
]. It is known that tea catechins modulate appetite and reduce food intake through the leptin receptor-independent pathway in rats [30
]. Also, green tea components have been reported to possess various biological and pharmacological effects, such as lowering of plasma lipids and glucose levels [31
In our repeated human trials (unpublished results), SPP enhanced physical stamina as shown in the animal studies [16
], leading to increases in appetite and outdoor activities. Since the increased physical activity enhanced food intake and thereby attenuated body weight loss, we added extracts of Garcinia cambogia
, white bean, mango, raspberry, cocoa, and green tea, possessing different mechanisms, to increase the anti-obesity effect and to control appetite. In the present study, we carried out an experiment to verify anti-obesity effects of Rapha diet® preparation containing the ingredients described above in an appropriate ratio, using a mouse model with dietary obesity.