Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues

Abstract

White adipose tissue (WAT) has key metabolic and endocrine functions and plays a role in regulating energy homeostasis and insulin sensitivity. WAT is characterised by its capacity to adapt and expand in response to surplus energy through processes of adipocyte hypertrophy and/or recruitment and proliferation of precursor cells in combination with vascular and extracellular matrix remodelling. However, in the context of sustained obesity, WAT undergoes fibro-inflammation, which compromises its functionality, contributing to increased risk of type 2 diabetes and cardiovascular diseases. Conversely, brown adipose tissue (BAT) and browning of WAT represent potential therapeutic approaches, since dysfunctional white adipocyte-induced lipid overspill can be halted by BAT/browning-mediated oxidative anti-lipotoxic effects. Better understanding of the cellular and molecular pathophysiological mechanisms regulating adipocyte size, number and depot-dependent expansion has become a focus of interest over recent decades. Here, we summarise the mechanisms contributing to adipose tissue (AT) plasticity and function including characteristics and cellular complexity of the various adipose depots and we discuss recent insights into AT origins, identification of adipose precursors, pathophysiological regulation of adipogenesis and its relation to WAT/BAT expandability in obesity and its associated comorbidities.

Heterogeneity of adipose tissue in development and metabolic function

“…In lean humans, subcutaneous adipocytes are larger than visceral adipocytes (Pellegrinelli et al, 2016), whereas the opposite is the case in mice (Sackmann-Sala et al, 2012;Schöttl et al, 2015) (Fig. 2).…”

MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

“…A recent study showed that regulation of lipid storage-related genes (DGAT2, SREBP1c and CIDEA) was defective in the subcutaneous adipose tissue of subjects exhibiting the largest fat accumulation in the visceral adipose tissue of non-obese subjects when overfed for 56 days, supporting the adipose tissue expandability theory (30). Apart from adipogenesis and lipogenesis, appropriate plasticity ensured by remodeling of the extracellular matrix and the vasculature are required for the maintenance of adipose tissue expandability (31).…”

“…We recently assessed in vivo mitochondrial function by 31 P-MRS after energy-depleting exercise in young healthy men born with a low birth weight (LBW) and at increased risk of developing T2D, and since diets high in fat and calories have been linked to mitochondrial dysfunction (89, 90), we investigated the potential effect of 5-day high-fat overfeeding. We found that in vivo mitochondrial function was not affected by overfeeding LBW individuals compared with that in controls (81), thereby not supporting the proposed hypothesis that high-fat diet induces alterations in mitochondrial function -not even in subjects at risk of developing insulin resistance and T2D.…”

Plasticity of adipose tissue in response to fasting and refeeding in male mice

“…WAT generally develops in discrete anatomical depots, identified as subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT); the distribution of fat is closely linked to metabolic disease risk [18, 19]. Emerging evidence has confirmed that the accumulation of VAT is closely related to the metabolic complications of obesity and cardiovascular disease [20–23].…”