Insulin, not surprisingly, is the primary regulator of LPL activity, although not the only one. This regulation functions differently, as is the case with all hormones, from tissue to tissue and site to site. In fat tissue, insulin increases LPL activity; in muscle tissue, it decreases activity. As a result, when insulin is secreted, fat is deposited in the fat tissue, and the muscles have to burn glucose for energy. When insulin levels drop, the LPL activity on the fat cells decreases and the LPL activity on the muscle cells increases—the fat cells release fatty acids, and the muscle cells take them up and burn them.

It’s the orchestration of LPL activity by insulin and other hormones that accounts for why some areas of the body will accumulate more fat than others, why the distribution of fat is different between men and women, and how these distributions change with age and, in women, with reproductive needs. Women have greater LPL activity in their adipose tissue than men do, for example, and this may be one reason why obesity and overweight are now more common in women than in men. In men, the activity of LPL is higher in the fat tissue of the abdominal region than in the fat tissue below the waist, which would explain why the typical male obesity takes the form of the beer belly. Women have more adipose-tissue LPL activity in the hips and buttocks than in the abdominal region, although after menopause the LPL activity in their abdominal region catches up to that of men.

These various fat deposits are also regulated over time by the changing flux of sex hormones, so LPL can be considered the point at which insulin and sex hormones interact to determine how and when we fatten. The male sex hormone testosterone, for instance, suppresses LPL activity in the abdominal fat, but has little or no effect on the LPL in the fat of the hips and buttocks. Increasing fat accumulation in the abdomen as men age may therefore be a product of both increasing insulin and decreasing testosterone. The female sex hormone progesterone increases the activity of LPL, particularly in the hips and buttocks, but estrogen, another female sex hormone, decreases LPL activity.*120 It’s the decrease in estrogen secretion during menopause—and so the increase in LPL activity—that may explain why women frequently gain weight as they pass through menopause. The effect of decreasing estrogen secretion on LPL activity would also explain why women typically fatten after the removal of the uterus in a hysterectomy. The change in hormonal regulation of LPL also explains how and why fat deposition changes during pregnancy and, after birth, with nursing.