Adipose tissue and metabolic syndrome: too much, too little or neither

Abstract

Obesity is strongly associated with metabolic syndrome. Recent research suggests that excess adipose tissue plays an important role in development of the syndrome. On the other hand, persons with a deficiency of adipose tissue (e.g. lipodystrophy) also manifest the metabolic syndrome. In some animal models, expansion of adipose tissue pools mitigates adverse metabolic components (e.g. insulin resistance, hyperglycaemia and dyslipidemia). Hence, there are conflicting data as to whether adipose tissue worsens the metabolic syndrome or protects against it. This conflict may relate partly to locations of adipose tissue pools. For instance, lower body adipose tissue may be protective whereas upper body adipose tissue may promote the syndrome. One view holds that in either case, the accumulation of ectopic fat in muscle and liver is the driving factor underlying the syndrome. If so, there may be some link between adipose tissue fat and ectopic fat. But the mechanisms underlying this connection are not clear. A stronger association appears to exist between excessive caloric intake and ectopic fat accumulation. Adipose tissue may act as a buffer to reduce the impact of excess energy consumption by fat storage; but once a constant weight has been achieved, it is unclear whether adipose tissue influences levels of ectopic fat. Another mechanism whereby adipose tissue could worsen the metabolic syndrome is through release of adipokines. This is an intriguing mechanism, but the impact of adipokines on metabolic syndrome risk factors is uncertain. Thus, many potential connections between adipose tissue and metabolic syndrome remain to unravelled.

Obesity and Cardiovascular Disease

“…The body defends from excessive caloric intake by increasing the storage of the white adipose tissue, resulting in obesity. However, when the increase in body weight stabilizes, the excessive caloric intake persists and the oxidative capacity of fat and lean mass cannot buffer the excess in caloric intake, ectopic fat will accumulate in muscle, liver, and other tissues, 106 which is well known to be a major determinant for MetS, and therefore for the MHO phenotype. 100 Strong support for the role of energy intake on the metabolic profile comes from bariatric surgery studies, 106 which have shown marked reductions in metabolic abnormalities (ie, people eat less after surgery) even in the presence of residual obesity.…”

Lean NAFLD: an Underrecognized Outlier

“…Using lipodystrophy as an example, the deficiency of adipose tissue leads to the redistribution of fat to skeletal muscle and liver with the resultant metabolic syndrome including severe insulin resistance (15). In these individuals, leptin deficiency induces overnutrition and leads to severe ectopic fat accumulation and resultant severe metabolic syndrome.…”

The size matters: regulation of lipid storage by lipid droplet dynamics

“…Excessive lipid storage in adipocytes results in hypoxia, ER stress, insufficient angiogenesis, increased adipocyte death, high immune cell infiltration, increased secretion of pro-inflammatory cytokines and the development of obesity and insulin resistance (Sell et al, 2012;Ye, 2013). On the other hand, insufficient lipid storage in adipose tissue under lipodystrophic condition leads to adipocyte lipotoxicity, mitochondrial dysfunction, increased oxidative stress, inflammatory responses, deregulated release of free fatty acids and impaired insulin sensitivity (Bindlish et al, 2015;Frayn, 2001;Grundy, 2015).…”