Abstract
Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in regulating systemic energy homeostasis. Adipose tissue expands by a combination of an increase in adipocyte size (hypertrophy) and number (hyperplasia). The recruitment and differentiation of adipose precursor cells in the subcutaneous adipose tissue (SAT), rather than merely inflating the cells, would be protective from the obesity-associated metabolic complications. In metabolically unhealthy obesity, the storage capacity of SAT, the largest WAT depot, is limited, and further caloric overload leads to the fat accumulation in ectopic tissues (e.g., liver, skeletal muscle, and heart) and in the visceral adipose depots, an event commonly defined as “lipotoxicity.” Excessive ectopic lipid accumulation leads to local inflammation and insulin resistance (IR). Indeed, overnutrition triggers uncontrolled inflammatory responses in WAT, leading to chronic low-grade inflammation, therefore fostering the progression of IR. This review summarizes the current knowledge on WAT dysfunction in obesity and its associated metabolic abnormalities, such as IR. A better understanding of the mechanisms regulating adipose tissue expansion in obesity is required for the development of future therapeutic approaches in obesity-associated metabolic complications.
Highlights
Severe obesity is associated with elevated risks of adverse health consequences
Findings showed that these mice are characterized by hepatic insulin resistance (IR) associated with an increased hepatic cytosolic diacylglycerols accumulation leading to the activation of protein kinase Cε (PKCε), which results in reduced IRS2 tyrosine phosphorylation and in the inability of insulin to activate hepatic glycogen synthesis and suppress hepatic glucose production [153]
The obesity pandemic has put a spotlight on adipocyte function, and we recognize it as an endocrine organ essential in regulating systemic energy homeostasis
Summary
Severe obesity is associated with elevated risks of adverse health consequences. The prevalence of obesity is rising worldwide, and if the trend continues, global prevalence will reach 18% in men and 21% in women by 2025 [1]. Using stable isotope methodology to measure SAT and VAT adipogenesis, Kim et al confirmed these observations and found a positive association between adipocyte turnover and insulin sensitivity They identified adipocyte hypertrophy as the major mechanism of adult fat mass expansion, supporting the concept that the failure of adipose tissue plasticity results in IR and metabolic disease [45]. These data indicate that both regional depositions of adipose tissue (visceral and/or subcutaneous) and adipocyte morphology (cell size; hypertrophy and/or hyperplasia) contribute to an increased risk of IR [38,57] In line with these findings, individuals with increased adipogenic capacity in SAT display a reduced adipose cell size and maintain a healthy metabolic state. The inadequate fat depots response to the caloric overflow leads to systemic metabolic alterations
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