Adipose Tissue Function and Expandability as Determinants of Lipotoxicity and the Metabolic Syndrome

Abstract

The adipose tissue organ is organised as distinct anatomical depots located all along the body axis and it is constituted of three different types of adipocytes : white, beige and brown which are integrated with vascular, immune, neural and extracellular stroma cells. These distinct adipocytes serve different specialised functions. The main function of white adipocytes is to ensure healthy storage of excess nutrients/energy and its rapid mobilisation to supply the demand of energy imposed by physiological cues in other organs, whereas brown and beige adipocytes are designed for heat production through uncoupling lipid oxidation from energy production. The concert action of the three type of adipocytes/tissues has been reported to ensure an optimal metabolic status in rodents. However, when one or multiple of these adipose depots become dysfunctional as a consequence of sustained lipid/nutrient overload, then insulin resistance and associated metabolic complications ensue. These metabolic alterations negatively affects the adipose tissue functionality and compromises global metabolic homeostasis. Optimising white adipose tissue expandability and its functional metabolic flexibility and/or promoting brown/beige mediated thermogenic activity counteracts obesity and its associated lipotoxic metabolic effects. The development of these therapeutic approaches requires a deep understanding of adipose tissue in all broad aspects. In this chapter we will discuss the characteristics of the different adipose tissue depots with respect to origins and precursors recruitment, plasticity, cellular composition and expandability capacity as well as molecular and metabolic signatures in both physiological and pathophysiological conditions.

Long‐term caloric restriction ameliorates deleterious effects of aging on white and brown adipose tissue plasticity

“…WAT is a critical regulator of systemic energy homeostasis, and its remodeling under pathophysiological and challenging conditions is linked to metabolic complications such as IR (Huh, Park, Ham, & Kim, ). AT plasticity in obesity, as well as in aging, involves tissue expandability (hypertrophy and/or hyperplasia), recruitment of inflammatory cells, and vascularization and innervation (Carobbio et al, ; Wang et al, ). Accretion of visceral, rather than scWAT, has been associated with the development of IR and metabolic syndrome; however, scWAT also must undergo expansion to accommodate an increased lipid supply to avoid ectopic lipid accumulation causing lipotoxicity.…”

“…Furthermore, increased adiposity by hypertrophy and/or hyperplasia has been demonstrated to increase macrophage infiltration. This circumstance, together with changes in adipocyte physiology that includes hypoxia, reticulum, and oxidative stress, leads to an inflammatory state which is a key factor in the AT expandability capacity (Carobbio, Pellegrinelli, & Vidal‐Puig, ). Nevertheless, AT is a complex organ with different localizations and functions beyond its traditional role as a fat storage unit.…”

A guide to studying human dermal adipocytes in situ

“…Adipose tissue is found within multiple body sites and can be divided into brown and white fat. The first is thought to be involved predominantly in thermogenesis, whereas the latter is recognized as a key player in whole‐body metabolism . An additional type of fat cells exists i.e.…”

p107 Deficiency Increases Energy Expenditure by Inducing Brown‐Fat Thermogenesis and Browning of White Adipose Tissue

“…These animals also have a leaner phenotype even when challenged with a high‐fat diet (HFD), something that is thought to be due to increased lipid oxidation in skeletal muscle, these observations have led to the nomination of p107 as a drug target for obesity . Nonetheless this idea may not be so straightforward because the lack of a weight gain in the absence of adipose tissue expansion can be associated with lipotoxicity in many tissues including endocrine pancreas and liver . Thus, we decided to investigate in detail the influence of p107 silencing in animals challenged with a HFD in terms of weight gain, adiposity, liver steatosis, and glucose intolerance.…”

“…[25] Nonetheless this idea may not be so straightforward because the lack of a weight gain in the absence of adipose tissue expansion can be associated with lipotoxicity in many tissues including endocrine pancreas and liver. [26][27][28] Thus, we decided to investigate in detail the influence of p107 silencing in animals challenged with a HFD in terms of weight gain, adiposity, liver steatosis, and glucose intolerance. Our data supports the hypothesis that mice lacking p107 are resistant to HFD, in terms of adiposity and weight gain.…”