Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways

Abstract

Lafontan M. Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways. Am J Physiol Cell Physiol 302: C327-C359, 2012. First published September 7, 2011; doi:10.1152/ajpcell.00168.2011.-For many years, there was little interest in the biochemistry or physiology of adipose tissue. It is now well recognized that adipocytes play an important dynamic role in metabolic regulation. They are able to sense metabolic states via their ability to perceive a large number of nervous and hormonal signals. They are also able to produce hormones, called adipokines, that affect nutrient intake, metabolism and energy expenditure. The report by Rodbell in 1964 that intact fat cells can be obtained by collagenase digestion of adipose tissue revolutionized studies on the hormonal regulation and metabolism of the fat cell. In the context of the advent of systems biology in the field of cell biology, the present seems an appropriate time to look back at the global contribution of the fat cell to cell biology knowledge. This review focuses on the very early approaches that used the fat cell as a tool to discover and understand various cellular mechanisms. Attention essentially focuses on the early investigations revealing the major contribution of mature fat cells and also fat cells originating from adipose cell lines to the discovery of major events related to hormone action (hormone receptors and transduction pathways involved in hormonal signaling) and mechanisms involved in metabolite processing (hexose uptake and uptake, storage, and efflux of fatty acids). Dormant preadipocytes exist in the stroma-vascular fraction of the adipose tissue of rodents and humans; cell culture systems have proven to be valuable models for the study of the processes involved in the formation of new fat cells. Finally, more recent insights into adipocyte secretion, a completely new role with major metabolic impact, are also briefly summarized. history; adipocytes; insulin action; 3T3-L1 cells; glucose transport; fatty acids; lipolysis; catecholamines; preadipocytes SINCE THE EARLIEST TIMES, attention has been directed toward fat-related questions. It is currently accepted that the ability to store fat in adipose tissue was a major advantage for survival during cold winters and periods of food shortage for our "primitive" hunter ancestors. However, in modern societies, with increased food availability and nutritional efficacy, excessive fat deposition is frequently associated with degenerative or metabolic diseases. As early as 1901, life insurance companies noted that excess weight, particularly around the abdomen, was linked to reduced life expectancy. The risk was confirmed in the seminal studies of Vague (366) in Marseilles, who established the importance of abdominal (central) obesity in conferring excess mortality. The health hazard of obesity is not considered in the present review, which, rather, focuses on adipose tissue and adipocytes.

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

“…Posttranslational cleavage of POMC by prohormone convertases generates several biologically active peptides classified as melanocortins. Beyond their central action via melanocortin receptors in the CNS, some melanocortins mediate their effects via melanocortin receptors in the periphery, of which α-melanocyte-stimulating hormone (αMSH) and corticotropin (adrenocorticotropic hormone, ACTH) are known for their significant pro-lipolytic action in adipocytes of rodents, as first reported in 1958 (Lafontan, 2012). In rodent adipocytes, ACTH binds to the melanocortin 2 receptor, which stimulates lipolysis via Gs-coupled cAMP-PKA-mediated phosphorylation of HSL (Cho et al, 2005) (Fig.…”

“…The enormous capacity for hypertrophy, i.e. cell expansion owing to fat storage, is a unique hallmark of adipocytes, as illustrated by maximal cell diameters in the range of 10-180 µm (Lafontan, 2012). The ability of adipose tissue to expand is further augmented by hyperplastic growth, which recruits adipocytes from a progenitor cell pool residing in stem cell niches of the tissue.…”

“…Without putting the dominant role of adrenergic signaling aside, a closer inspection and functional evaluation of other ligands, receptors and intracellular signaling pathways in the control of lipolysis in adipocytes seems to be a rewarding exercise, promising new insights into lipid metabolism and energy balance physiology. Our reviews of the published literature revealed several non-adrenergic biomolecules that have been identified to effect lipolysis in white adipocytes, only a few of which have been examined for their lipolytic action in brown and brite adipocytes (Duncan et al, 2007;Lafontan, 2012). As a working hypothesis, any stimulus affecting the balance of lipolysis and re-esterification potentially attenuates or activates thermogenesis in brown and brite adipocytes (Fig.…”

A new role for extracellular vesicles: how small vesicles can feed tumors' big appetite

“…In addition to their most well-known role of storing FAs in the form of TGs and releasing them to supply energy when needed, adipocytes are also powerful endocrine cells. Indeed, they secrete a large panel of bioactive molecules, named adipokines, including hormones, growth factors, chemokines and pro-inflammatory molecules, whose balance is perturbed in obesity (123,124). Due to the distribution of adipose tissue (AT), many cancer cells will come into contact with adipocytes during local invasion (for example in breast, colon and prostate cancers, as well as melanoma) but also distant dissemination (to the omental fat for gastric and ovarian cancer, but also to the bone marrow) (125,126).…”

Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology

“…These cells are recruited from various populations of multipotent stem cells/progenitors. In the past two decades, there has been an explosion of research dealing with the biology of stem cells derived from adipose tissue, showing that a diverse subset of multipotent stem cells can contribute to adipose tissue homeostasis (Lafontan, 2012;Dodson et al, 2015). The diversity of stem cell populations, the biological fates of each of these populations depending on the tissues where they are issued, and the flexibility in abundance and properties of these cell populations are thus bottlenecks to consider for a better understanding of the mechanisms governing adipose tissue development.…”