What we talk about when we talk about fat

Abstract

There has been an upsurge of interest in the adipocyte coincident with the onset of the obesity epidemic and the realization that adipose tissue plays a major role in the regulation of metabolic function. The past few years, in particular, have seen significant changes in the way that we classify adipocytes and how we view adipose development and differentiation. We have new perspective on the roles played by adipocytes in a variety of homeostatic processes and on the mechanisms used by adipocytes to communicate with other tissues. Finally, there has been significant progress in understanding how these relationships are altered during metabolic disease and how they might be manipulated to restore metabolic health.

Figure 1. Interest in adipose biology has risen over time

Papers were identified in Pubmed using the term “adipose” for each year from 1900-2012 and expressed as total number of adipose papers (blue) and adipose papers as a percentage of all papers (red). Important events in adipose biology research are indicated by publication date. We are now in the midst of the second surge of interest in adipose biology in the last century.

Figure 2. Different origins for distinct types of adipocyte

White and beige adipocytes derive from Pax7-/Myf5- cells, via distinct precursor cells. Beige adipocytes differentiate following activation by cold or other inducers. After cold challenge is removed, these cells become inactive, taking on the morphology of a ‘white’ adipocyte. Classic brown fat, in contrast, comes from a Pax7⁺/Myf5⁺ lineage shared with skeletal muscle.

Figure 3. Activators of beige/brown fat development and function

Many inducers of browning and enhanced thermogenesis have been discovered. Some of these agents appear to work primarily by inducing the formation of new beige (e.g. irisin) or brown (e,g. BMP7) adipocytes while others may act on both recruitment and enhancement of thermogenic potential.

Figure 4. Immune cells are integral components of the fat pad in leanness and obesity

The lean fat depot contains many types of immune cell, dominated by resident M2 macrophages, eosinophils, and Tregs. In the setting of overnutrition, there is accumulation of proinflammatory cells, including M1 macrophages, mast cells, and various T lymphocyte classes.

Figure 5. Adipocyte-matrix interactions play a role in the pathology of obesity

Adipocytes secrete numerous matrix proteins that maintain the structure of the depot. During overnutrition, adipocytes increase in size until further expansion becomes limited by the matrix, which undergoes fibrotic changes. This triggers changes that include hypoxia, inflammation, and cell death, all of which contribute to insulin resistance.

Figure 6. Adipose cross-talk with other tissues

Adipocytes store and release calories to the body generally, but numerous examples have emerged demonstrating additional roles of fat in a wide array of biological processes. These examples given here are illustrative, and not exhaustive.