Fat cell apoptosis
Inventors
Dr. Gary Weisinger, Dr. Rona Limor & Prof. Naftali Stern, Director,
Institute Endocrinology, Metabolism and Hypertension Tel Aviv
Medical Center
Background, highlights & our innovation:
Obesity has become a global epidemic afflicting both children and adults, and
gradually spreading from the Western countries to the developing nations as well. It is
now widely recognized that obesity is associated with and is actually a major culprit
in numerous co-morbidites, e.g. heart disease, type 2 diabetes, hypertension some
cancers and sleep apnea. The current invention proposes a new approach to lowering
weight in obesity, by specifically reducing the number of fat cells using a biological
type treatment.
This invention induces weight loss in obese or overweight individuals via the
induction of programmed cell death in fat cells and pre-adipocytes using in vivo
knockout therapy of the enzyme, platelet-type 12 lipoxygenase (12LO), by the
delivery of a 12LO antisense construct driven by a fat–cell specific
promoter/enhancer . Data generated in our laboratory which provides support for the
following strategy, has been developed:
1) Platelet-type human 12-LO is expressed in fat cells and pre-adipocytes and
functions as an anti-apoptotic system in these cells.
2) Platelet-type 12-LO knockout of adipocytes results in apoptotic cell death that can
be prevented, in part, by the addition of exogenous 12 hydroxyeicosatetraenoic acid
(HETE), the enzymatic product of 12LO.
3) Apoptotic cell death can be used to reduce fat cell number and thereby, fat mass
and weight in overweight or obese subjects.
4) Restriction of the induction of apoptosis to fat cells can be accomplished by 12LO
antisense constructs driven by promoter/enhancer units of genes expressed
exclusively in fat cells such as the adiponectin gene.
5) Fat-specific 12LO antisense knockout therapy can be delivered in the form of
liposomes or any other method of physical /chemical packaging of the treatment
construct or through viral vectors such as the gutless adenovirus- or gutless adenoassociated virus or retroviral moieties already in use for human gene therapy.
6) Because the induced apoptotic effect is not massive. Damage resulting from abrupt
overflow of free fatty acid and / or triglycerides can be minimized and treatment can
be repeated until desirable outcome is attained.
THE PATENT APPLICATION no. PCT/IL2007/001333