The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 7 No.
1 • February 2004
Angiogenesis Inhibitors May Control Fat Tissue—New Blood Vessels Support Fat Growth
New understanding of how fat tissue grows suggests possible new ways to inhibit it. Recent studies suggest that adipose (fat) tissue depends upon its blood supply in order to maintain its mass. Although most blood vessels in an adult are mature and not growing, adipose tissue can expand and contract throughout life, and its blood vessels can grow to meet the needs of larger adipose stores or regress when adipose stores become smaller. The growth-stimulatory effect on endothelial cells of adipose blood vessels when cultured with preadipocytes (immature fat cells) appears to affect no other cell type.
Adipocytes and endothelial cells interact with each other. Adipocytes, for example, produce and release growth factors such as vascular endothelial growth factor (VEGF), monobutyrin, and leptin, all of which promote the proliferation of endothelial cells. At the same time, endothelial cells secrete factors that promote and support the proliferation of preadipocytes, such as basic fibroblast growth factor and platelet-derived endothelial-cell growth factor. In an animal model, weight regain taking place after weight loss on a food-restricted diet resulted in increased angiogenic activity in the adipose tissue mass, due to the induction of VEGF.
In a recent paper, scientists investigating the sensitivity of adipose tissue (in ob/ob mice, which accumulate fat mass rapidly) to antiangiogenic drugs found that the suppression of endothelial cell proliferation by the drugs resulted in a significantly lower adipose tissue mass. In fact, in the ob/ob mice, which lack leptin, the antiangiogenic drugs had similar effects in reducing fat mass as did treatment with leptin. The researchers also found that weight reduction from angiogenesis inhibitors, leptin, or calorie-restricted diets were all associated with adipose endothelial cell apoptosis (programmed cell death). Moreover, they found that endothelial cells in mature tissues (that have reached their adult size and do not continue to grow) were not responsive to antiangiogenic drugs, while the endothelial cells in adipose tissue were responsive. (Interestingly, the vasculature of hair follicles also expands during the growth phase, decreasing during the rest phase. There is also vascular growth in inflammatory skin diseases, such as psoriaris.)
A recent paper even suggests that angiogenesis is associated with Alzheimer’s disease, showing vascular basement membranes from Alzheimer’s disease and normal brain that reveal much higher microvascular density in the Alzheimer’s brain. The authors suggest that anti-inflammatory drugs, H2-receptor blockers, antihypertensives, and statins may reduce the risk of Alzheimer’s via their antiangiogenic effects.
There are many natural substances with antiangiogenic properties, for example, green tea and epigallocatechin-3-gallate (EGCG, a constituent of green tea), flavonoids found in edible berries, curcumin (comprising about 40% of the spice turmeric), genistein, fisetin, and luteolin, and resveratrol (found in grapes and red wine). While it would appear that nobody has done a weight-control study in humans using dietary increase of antiangiogenic foods (and possibly nobody ever will, because of the high costs of such a study and the unpatentability of natural substances), increasing dietary intakes of substances such as those mentioned here might help and is unlikely to hurt.
- Rupnick et al. Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci 99(16):10730-5 (2002).
- Liu and Meydani. Angiogenesis inhibitors may regulate adiposity. Nutr Rev 61(11):384-7 (2003).
- Roy et al. Anti-angiogenic property of edible berries. Free Rad Res 36(9):1023-31 (2002).
- Vagnucci and Li. Alzheimer’s disease and angiogenesis. Lancet 361:605-8 (2003).
- Cao and Cao. Angiogenesis inhibited by drinking tea. Nature 398:381 (1999).
- Gururaj et al. Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem Biophys Res Comm 297:934-42 (2002).
- Joussen et al. Treatment of corneal neovascularization with dietary isoflavonoids and flavonoids. Exp Eye Res 71:483-7 (2000).