Tocopherol and Tocotrienol
Anti-Obesity Medicaments

Case Number CH-034

Inventors: Bruce Ames, PhD, et al.

Patent No. Title Issue Date Country
Pending Tocopherol and Tocotrienol Anti-Obesity Medicaments   United States
Pending     PCR

Abstract
The invention provides methods and compositions for reducing triglyceride accumulation in adipocytes, particularly accumulation resulting from obesity-promoting drug use.

Vitamin E consists of eight compounds: four tocopherols (alpha-, beta-, gamma-, and delta-); and four tocotrienols (alpha-, beta-, gamma-, and delta-). Among them, only alpha-tocopherol has been extensively studied. Gamma-tocopherol is the major form of vitamin E in the US diet. However it has drawn little attention compared with alpha-tocopherol, the primary form of vitamin E found in most supplements. Delta-tocopherol is another form of vitamin E that is rich in some food sources (also found with gamma-tocopherol, e.g. in soybeans and soybean oil). Tocotrienols are mainly abundant in palm oil.

Chronic use of a number of medications is known to contribute to obesity. For example, the treatment of diabetes using anti-diabetes drugs, including the thiazolidinedione class (troglitazone, rosiglitazone and proglitazone) commonly leads to weight gain and obesity (Malinowski JM et al, 2000, Clinical Therapeutics, 22, 1151-68). UK Prospective Diabetes Study has clearly demonstrated that weight gain associated with diabetes treatment partially cancels the beneficial effects of tight blood glucose control on cardiovascular events and mortality (UK Prospective Diabetes Study, Group, 1998, Lancet, 352, 854-65).

Ishermann et al. 1999, Diabetes Care 22, 1227-1228 report that alpha-tocopherol induces leptin expression in healthy individuals; Ohrvall et al. J. Internal Med 1993, July:234(1): 53-60 report lower tocopherol serum levels in subjects with abdominal adiposity; Sjoholm et al., Biochem Biophys Res Commun 2000, Oct 22;227(2):334-40, report that gamma tocopherol partially protects insulin-secreting cells against functional inhibition by nitric oxide.

Advantage
We have found that tocopherols, particularly gamma-T and delta-T, and tocotrienols, particularly, alpha-, gamma-, and delta-, show dose-dependent anti-adipogenesis activity.  The compounds ameliorate high fat diet-induced obesity and type 2 diabetes in mice.  Thus, our methods and compositions provide for inhibiting or reducing triglyceride accumulation in adipocytes, or any manifestations thereof, and/or reducing the likelihood of developing, and promoting resistance to undesirable or excess triglyceride accumulation in adipocytes.

Related Publications

Contact:
Technology Transfer Office Phone (510) 428-3885, ext. 5103