Cellular and molecular factors in adipose tissue growth and obesity.

Heparin-binding growth factors related to basic fibroblast growth factor are major determinants of the cellular clonal composition of adipose tissue. By providing and maintaining varying complements of preadipocytes in different fat depots, these factors contribute to the varying sizes and functions of different regions, including the hypercellularity in appreciable obesity. Thus, differing levels and activities of the heparin-binding growth factors contribute to variations in depots within the same individual and between individuals, in lean and obese states. In contrast to regional differences in adiposity, which are accounted by factors resident in adipose tissue, we believe that obesity results from a generalized energy overload. According to our concept, there are genetic variations in cytoskeletal activity and thus differing quantities of energy are utilized for biomechanical processes. In a reciprocal relationship, the higher the cytoskeletal activity, the lesser the energy available for chemical energy storage, mainly in the form of triglyceride in adipocytes. At the extreme of "supermassive" obesity, a mutation in a gene related to a cytoskeletal protein would lead to appreciable dampening of cytoskeletal activity, with consequently the greatest quantity of energy remaining available for eventual triglyceride storage. Moreover, the new concept, for which we have have increasing experimental evidence, invokes a hypothalamic-efferent neural-cytoskeletal pathway, which would modulate the activity of the cytoskeleton.