Adipose tissue remodeling and obesity

Abstract

To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state. As such, the tissue requires potent mechanisms to remodel, acutely and chronically. Adipocytes can rapidly reach the diffusional limit of oxygen during growth; hypoxia is therefore an early determinant that limits healthy expansion. Proper expansion requires a highly coordinated response among many different cell types, including endothelial precursor cells, immune cells, and preadipocytes. There are therefore remarkable similarities between adipose expansion and growth of solid tumors, a phenomenon that presents both an opportunity and a challenge, since pharmacological interventions supporting healthy adipose tissue adaptation can also facilitate tumor growth. IntroductionAdipose tissue (AT) can respond rapidly and dynamically to alterations in nutrient deprivation and excess through adipocyte hypertrophy and hyperplasia, thereby fulfilling its major role in wholebody energy homeostasis. AT remodeling is an ongoing process that is pathologically accelerated in the obese state, and thus, features such as reduced angiogenic remodeling, ECM overproduction, a heightened state of immune cell infiltration and subsequent proinflammatory responses prevail in many obese fat-pads (1). However, not all AT expansion is necessarily associated with pathological changes. The concept of the "metabolically healthy obese" state (2) suggests that some individuals can preserve systemic insulin sensitivity on the basis of "healthy" AT expansion, bypassing all of the aforementioned pathological consequences associated with obesity (3), thereby also avoiding the obesity-associated lipotoxic side effects. Many physiologically relevant processes important for human AT remodeling can be studied in rodent models, with the added advantage that processes related to AT expansion and reduction can occur at an extremely rapid rate. A 24-hour fast in a mouse is associated with a dramatic loss of AT mass and an acute remodeling process that involves rapid infiltration of macrophages; moreover, merely 24 to 48 hours of exposure to a high-fat diet (HFD) can cause a prompt increase in adipocyte size (4). AT is therefore an ideal model system to study rapid alterations in tissue expansion and reduction, as it adapts to a differential nutrient supply. Here, we will focus on key aspects of the intricate dynamics of AT remodeling and subsequent inflammatory consequences that arise from obesity.

Adipose tissue inflammation and ectopic lipid accumulation [Review]

“…In this regard, Khan et al reported that mice lacking collagen VI, which is expressed abundantly in adipose tissue, exhibit the uninhibited adipose tissue expansion and substantial improvements in insulin sensitivity on a high-fat diet [67]. These findings suggest that reduced lipid storage in obese adipose tissue may contribute to ectopic lipid accumulation in non-adipose tissues such as the liver, skeletal muscle, and pancreas, where lipotoxicity impairs their metabolic functions [10,[71][72][73]. Although the molecular mechanisms underlying adipose tissue fibrosis are still largely unknown, recent evidence suggests that a PPARγ-fibroblast growth factor 1 (FGF1) axis is required for obesity-induced adipose tissue remodeling [74].…”

“…In other words, stromal cells change dramatically in number and cell type during the course of obesity. Such dynamic histological changes observed in obese adipose tissue can be referred to as "adipose tissue remodeling" [10,17,18]. In this regard, recent evidence suggests that the interaction between mature adipocytes and stromal cells in adipose tissue plays a critical role in the regulation of adipocytokine production [18].…”

“…It is also known that, in addition to mature adipocytes, stromal cells are also important sources of certain adipocytokines such as tumor necrosis factor-α (TNFα). This is reminiscent of the chronic inflammatory responses in atherosclerotic vascular walls termed "vascular remodeling", which is mediated through complex interactions among vascular endothelial cells, vascular smooth muscle cells, obesity to store triglyceride effectively in adipose tissue [10]. When adipose tissue cannot meet the demand of storing excessive energy, triglyceride is accumulated in non-adipose tissues as ectopic fat, which may lead to insulin resistance in the liver and skeletal muscle and insufficient insulin secretion in the pancreas (lipotoxicity) [10,11] (Fig.…”

Cachexia-associated adipose tissue morphological rearrangement in gastrointestinal cancer patients

“…Several chronic diseases, such as obesity,20 metabolic syndrome and lipodystrophy,21 induce AT remodelling, involving two major processes: adipose cell morphometric changes (hypertrophy or atrophy) and immune cells accumulation. Inflammation, endoplasmatic reticulum stress and hypoxia are also part of the general biologic alterations subsidizing the attraction and retention of inflammatory cells in AT 22.…”

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

“…Moreover, excess of nutrients causes an increase in the size (hypertrophy) and number (hyperplasia) of adipocytes during the development of obesity (Sun et al 2011). However, the ability of AT to store excess energy as triglycerides is limited, as determined by both genetic and environmental factors.…”