What is Adipotide?

Adipotide is a peptidomimetic compound that has been shown to possess pro-apoptotic properties that do cause weight loss in rhesus monkeys and mice. Its sequence is CKGGRAKDC-GG-D(KLAKLAK)2. Studies have shown that its mode of action involves the selective apoptosis of blood vessels supplying the white adipose tissue. Adipotide causes such vessels to undergo atrophy (shrinkage) and eventually apoptosis (cell death), thus cutting off the blood supply to the fat cells. This results in ischemic injury, which is a lack of blood supply and oxygen to the fat cells. The effects are non-reversible, so the fat cells also undergo apoptosis or cell death.

Molecular analysis has shown that the stereo-chemical structure of Adipotide enables it to bind to two specific receptors that are exclusively found in blood vessels that supply white adipose tissue. These receptors are prohibitin and ANXA-2. Due to the tissue specificity of these receptors, Adipotide does not have any effect on the brown adipose tissue, thus it does not affect the adaptive brown fat thermogenesis. Brown fat thermogenesis is especially vital for babies because they have limited capacity for heat conservation as the body surface area to volume ration favors high rates of heat loss. The white adipose tissue is formed only when energy consumption exceeds energy utilization.

Obesity

In 2008, epidemiological studies showed that 33.9% of the total American adult population is affected by obesity. Obesity results from excess adipose tissue mass. Studies have shown that white adipose tissue is the main cause of obesity. An increase in body weight does not equate to obesity since such an increase could result from an increase in the lean body mass and not necessarily due to increased adiposity. Obesity is associated with an increase in morbidity and mortality rates. Currently, obesity is gauged using the BMI (Body Mass Index), anthropometry (using skinfold thickness) and densitometry. The threshold for obesity is set at a BMI of 30. Increased adiposity predisposes the affected individual to a myriad of pathologies such as hypertension, hyperlipidemia, metabolic syndrome, NIDDM (Non-Insulin Dependent Diabetes Mellitus), cerebrovascular accidents, myocardial infarction and cancers. The distribution of adiposity does determine the morbidity rate, for instance abdominal adiposity causes more morbidity than adiposity localized to the buttocks and lower limbs. Therefore, the waist-to-hip ratio is used clinically to determine the probability of a person being affected by the pathologies stated above. The association between abdominal adiposity to increased morbidity is attributed to the fact that intra-abdominal adipocytes possess more lipolytic activity as compared to adipocytes located in the lower limbs.

Adipose tissue is made up of adipocytes (lipid-storing adipose cells) and the vascular/stromal compartment where macrophages and preadipocytes reside. Hypertrophy of adipose cells due to increased lipid deposition, and their subsequent hyperplasia do result in an increase in adipose mass. Such an increase is also characterized by high numbers of infiltrating macrophages and increased differentiation of preadipocytes to adipocytes. Such differentiation and maintenance of an increased adipose mass is sustained by an intact blood supply to the adipose tissue. Ischemic injury to such an adipose tissue would inhibit differentiation and activate apoptotic cascades in the injured adipocytes. Therefore, a peptidomimetic such as Adipotide would cause a reduction in adipose mass by causing non-reversible ischemic injury to adipocytes located in white adipose tissue.

Conclusion

Adipotide is a peptidomimetic compound [sequence CKGGRAKDC-GG-D(KLAKLAK)2] that possesses pro-apoptotic and lipolytic properties which enables it to act as an anti-obesity peptide. Studies have shown that its mode of action involves selective apoptosis of the vasculature of the white adipose tissue. This results in apoptosis in the white fat cells, thus reducing the overall adipose mass.