Chapter 47
Obesity and Diabetes — 6
Figure 4.1. Fat cells (adipocytes) are a tiny fraction of our body’s cells (upper panel) but comprise a dominant part of our cell biomass (lower panel). Adapted from Ian Hatton et al., “The human cell count and size distribution,” Proceedings of the National Academy of Sciences of the USA 120, no. 39 (September 2023): e2303077120, https://doi.org/10.1073/pnas.2303077120.
Adipocytes comprise a relatively tiny proportion of our thirty-seven trillion cells by count (upper panel above), but by mass they are overwhelmingly the dominant component, and almost all of that is white fat tissue.
In contrast, brown fat is a tiny fraction of our fat mass, only 0.2 to 3 percent; it consumes glucose and triglycerides to generate heat. Even that small amount declines with age and with increased ambient temperatures. White adipocytes secrete factors (adipokines) that communicate with organs including the brain. Some reduce sensitivity to insulin. Some activate the immune system. Most of these factors are pro-inflammatory, which is why I tell my patients that belly fat serves as the reservoir, the machinery, for promoting inflammation throughout the body. Indeed, decades of research on waist circumference has shown it is a highly informative metric and should be used as a vital sign in routine clinical practice, but sadly that has not ever caught on.
Obesity is simply way too much white adipose tissue. Unfortunately, unlike any other cell in our body, white fat cells can increase their volume by more than a factor of ten! And compared with all the other types of cells in the body, look how big (fig. 4.2) they are before that exceptional capability of an order of magnitude expansion.
In a study of people who were overweight or obese, the more brown fat tissue, the more they were metabolically healthy by a variety of metrics, including ability to generate heat after food intake. If only we could activate our relatively scant brown fat cells, as has been done in a small group of people with a β3-adrenergic receptor agonist (mirabegron), which led to less insulin resistance, more insulin secretion, and better blood lipid results such as higher HDL and ApoA1. Perhaps we’ll see more work to take advantage of the switch from white to brown fat in the future. In the meantime, albeit in small quantities, there’s a third cell type in fat tissue—beige cells—that are scattered within white fat tissue and can be switched into brown with exercise or need for heat production. Exciting recent discoveries of a molecule that controls the size of brown and beige adipose tissue, and conversion of white to beige fat, paves the way for a drug that will prevent age-related decline.