Compositions and methods for treating obesity, obesity related disorders and for inhibiting the infectivity of human immunodeficiency virus

Abstract

The present invention relates to methods and pharmaceutical compositions for treating obesity or obesity-related disorders in a subject suffering from or predisposed to developing obesity or an obesity-related disorder, or for inhibiting the infectivity of HIV, by administering oleuropein, an analogue or derivative thereof, or the major metabolites of oleuropein including oleuropein aglycone, hydroxytyrosol, and elenolic acid or their analogues, or derivatives thereof, an iridoid glycoside, or a secoiridoid glycoside or analogues or derivatives thereof, or any combination of the foregoing including olive leave extract. The invention also relates to methods for screening / diagnosing a subject having, or predisposed to having obesity or a related disorder by measuring the expression profiles of an adipogenic gene selected from PPARγ2, LPL and αP2 gene and gene product, or other adipogenic, lipogenic, or lipolytic genes and gene products in an individual. The invention further provides for screening for novel oleuropein analogues.

Description

FIELD OF THE INVENTION[0001]The present invention relates generally to methods and compositions for modulating the body weight of mammals including animals and humans, and more particularly to materials identified herein as modulators of weight, and the use of these materials for treating obesity and disorders related to obesity and to the diagnostic and therapeutic uses to which such modulators may be put. The present invention also relates to methods and compositions for inhibiting the infectivity of human immunodeficiency virus (HIV).BACKGROUND OF THE INVENTION[0002]Obesity, which is defined in general terms as an excess of body fat relative to lean body mass, is now a world wide epidemic, and is one of the most serious contributors to increased morbidity and mortality. Obesity is prevalent in the United States, affecting more than 61% of the total population (Flegal, et al., Overweight and Obesity in the United States: Prevalence and Trends, 1960-1994. Int J Obes 22:39-47, 1998)...

AI Technical Summary

Benefits of technology

[0006]In accordance with the broadest aspect of the invention, methods and compositions comprising oleuropein, or an analogue or derivative thereof, or the major metabolites of oleuropein including oleuropein aglycone, hydroxytyrosol, and elenolic acid or their analogues, or derivatives thereof, or an iridoid glycoside, or a secoiridoid glycoside or their analogues or derivatives thereof, or any combination of the foregoing including but not limited to olive leave extract, are disclosed for treating obesity and obesity-related conditions or disorders, as well as for inhibiting the infectivity of HIV. In particular, these compositions modulate adipogenesis, lipodystrophy, reduce fat accumulation and weight gain. These agents also prevent HIV viral fusion/entry into a host cell and bind the catalytic site of the HIV integrase. Thus, these agents provide an advantage over other anti-viral therapies in that both viral entry and integration are inhibited. They exert their effect by modulating adipocyte differentiation (adipogenesis), de-differentiation, transdifferentiation, and by decreasing the number of adipocytes (fat cells), or by modulating adipocyte metabolism (lipid synthesis, storage, accumulation, and utilization) so as to decrease fat accumulation and decrease the size of the fat cell (decrease fat mass), increase fat burning and expenditure. These compositions also have an effect on adipogenic, lipogenic and lipolytic gene/gene product expression, perturbation of pre-adipocyte to ad...

Problems solved by technology

Obesity, which is defined in general terms as an excess of body fat relative to lean body mass, is now a world wide epidemic, and is one of the most serious contributors to increased morbidity and mortality.

These abnormalities predispose the vasculature to injury, cellular proliferation and lipid oxidation, with resulting atherosclerosis leading to heart attack, stroke, and peripheral vascular diseases.

Thus, obesity and its associated complications continue to be a major problem throughout the worldwide health care system.

To date, these approaches have been limited to diet and exercise (therapeutic lifestyle changes), surgical procedures such as gastric bypass, and pharmacologic agents.

Drug treatment for obesity has been disappointing since almost all drug treatments for obesity are associated with undesirable side effects that contributed to their termination.

Although body weight loss is effective, these sympathomimetic drugs cause side effects including pulmonary hypertension, neuroanatomic changes, and a typical valvular heart diseases.

However, long-term success of dietary regulation is low because of noncompliance.

The loss of motivation to change dietary habits necessary to consume less fat and fewer calories results in regaining weight.

Thus, there are no real treatments based on the biology of the primary metabolic abnormalities found in obesity and its related conditions, such as metabolic syndrome or atherosclerosis.

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