Molecular Regulation and Therapeutic Potential of Thermogenic Fat Cells

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Background

Much of systemic metabolism depends on the activity and function of adipose tissue. Adipocytes in mammals fall into two categories classified by their primary functions: white fat cells that mediate energy storage and thermogenic fat cells that counteract hypothermia and obesity through adaptive thermogenesis. Whereas white fat and its function as an energy reservoir and endocrine organ have been studied for decades and are relatively well understood, until recently many aspects of the thermogenic fat biology have remained elusive.

The last decade has witnessed an explosion of interest and studies focusing on the regulation of thermogenic fat and potential therapeutics targeting these adipocytes. Some groundbreaking discoveries have led to our current understanding of thermogenic fat biology. Accumulating evidence supports the hypothesis that thermogenic fat cells arise from at least two different developmental origins: the ones of a skeletal muscle-like lineage are now called “classical” brown fat cells, and the rest of the thermogenic fat cells are normally referred to as the beige/brite (brown in white) fat cells. Definitions of types and/or subtypes of thermogenic fat cells will continue to evolve as further studies reveal distinctive functions of these cells. Many recent and ongoing studies have provided key insights regarding how adaptive thermogenesis is mediated in these unique adipocytes, particularly, how the mitochondrial function is regulated. Similar to white fat, thermogenic adipocytes closely communicate with other cells and organs, and these constant information exchanges are conducted through circulating secreted molecules (both hormones and metabolites) as well as autocrine/paracrine factors within the adipose tissue niche. Central control also plays an essential role in regulating the development and activation of thermogenic fat cells through sympathetic innervation and other mechanisms. The rediscovery of thermogenic fat cells in human adults ignited enthusiasm towards these cells serving as novel therapeutic targets against obesity and its associated metabolic disorders. One of the key questions is whether the average amount and activity of these cells in the adult human is sufficient to influence whole body metabolism. Emerging data is starting to address this as several recent reports have demonstrated that activated thermogenic fat cells help to improve glucose tolerance and insulin sensitivity in humans.

In this research topic we will summarize the recent advancements in our understanding of these metabolically active fat cells. We will focus our discussions in the following areas:

1. Developmental origins of thermogenic fat cells (brown fat, beige/brite fat, white fat, and other potentially distinct type(s) of fat cells, e.g. marrow fat).
2. Mechanistic insights on the regulation of thermogenic fat cells (Mitochondrial function, fuel sources of thermogenic fat cells, etc.).
3. Secretory molecules that regulate thermogenic fat functions (metabolites and adipokines).
4. Central control of the adaptive thermogenesis and other functions of thermogenic adipocytes (sympathetic innervation and brain-fat communications).
5. Regulation of thermogenic fat cells and their therapeutic potential in humans

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