Time and again, as we study physiologic phenomena and their anatomic correlates, greater clarity comes from realizing that heterogeneous wholes are composed of somewhat more homogeneous parts and from examining the independent and interactive effects or associations of these parts with outcomes of interest. For example, whereas previously we analyzed total cholesterol and its association with health, few scientists today would not measure separately the HDL and LDL cholesterol (as well as other components and subfractions), given their opposite effects on cardiovascular disease risk. Similarly, recent authors (1) teach us that not all fatty acids can be lumped in a single category of fat when we consider the effects of dietary fat intake. More than 150 y ago, when Quetelet developed the body mass index, expressed as weight divided by the square of stature, one might have wondered why he did not divide by the cube of stature. Indeed, because people are 3-dimensional beings, one might expect weight to increase in proportion to the cube of stature. This would be so if people were spheres of uniform density. However, it so happens that, among adults (who are not spheres of uniform density), weight increases approximately in proportion to the square of stature. Quetelet's early observation foreshadowed the importance of considering tissue heterogeneity in obesity research. More than half a century ago, Vague (2) helped us realize that, by differentiating among anatomical depots of fat, we could better appreciate the health effects of adiposity. That fecund observation has been a driving force in our field ever since.
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