Thermogenic Compositions and Methods
Biologicals for treatment of obesity related disease, including glucose intolerance and neurological disorders.
Worldwide obesity has tripled over the last 40 years and the incidence of overweight or obese populations is rising in low, middle, and high income countries. An increase in adipose tissue results in higher risk for cardiovascular disease and type 2 diabetes, which increase risk for Alzheimer’s disease and related dementias. Patients with high accumulations of intra-abdominal (iAb) fat are also at risk of developing insulin resistance. Efforts to treat obesity resulting from an increase in iAb adipose tissue have only had marginal success, in part due to the complex multifactorial nature of the disorder.
Thermogenic adipose tissue can improve energy balance and prevent metabolic pathogenesis, thus presenting a method of reducing obesity that does not rely on a patient’s “will-power” or complicated dietary compliance.
Dr. Ouliana Ziouzenkova and Dr. Jonathan Parquette, researchers at The Ohio State University, have identified several molecules that induce thermogenesis, a key process for control of obesity and glucose tolerance. The use of these pharmaceutical compositions, either alone or in combination of two or more in a pharmaceutical acceptable carrier could be formulated to treat or prevent diseases associated with iAb fat accumulation, promote glucose uptake in peripheral tissues, induce leptin secretion, control insulin resistance, and enhance innervation.
As a proof-of-concept, in vivo effects of the compounds were examined in WT mice with high-fat diet-induced obesity. Injections of the compound into iAb fat for two weeks had profound effects on body temperature in the abdominal area of these mice. The increase in body temperature correlated with an increase in metabolic rate and prevented weight gain.
The compounds may be delivered through a biocompatible nanostructure that is formed from short peptides that self-assemble into small nanofibers (~10 nm). Nanofibers enhance efficacy of compounds by improving their stability, offering antioxidant protection, and inducing leptin signaling pathway. Additionally, the combination therapy can be formulated for delayed release or a release in adipose tissue for locally targeted treatment.