Adipose Tissue Remodeling in Obesity: An Overview of the Actions of Thyroid Hormones and Their Derivatives

Abstract

Metabolic syndrome and obesity have become important health issues of epidemic proportions and are often the cause of related pathologies such as type 2 diabetes (T2DM), hypertension, and cardiovascular disease. Adipose tissues (ATs) are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. An ample body of evidence indicates that in some pathophysiological conditions, the aberrant remodeling of adipose tissue may provoke dysregulation in the production of various adipocytokines and metabolites, thus leading to disorders in metabolic organs. Thyroid hormones (THs) and some of their derivatives, such as 3,5-diiodo-l-thyronine (T2), exert numerous functions in a variety of tissues, including adipose tissues. It is known that they can improve serum lipid profiles and reduce fat accumulation. The thyroid hormone acts on the brown and/or white adipose tissues to induce uncoupled respiration through the induction of the uncoupling protein 1 (UCP1) to generate heat. Multitudinous investigations suggest that 3,3′,5-triiodothyronine (T3) induces the recruitment of brown adipocytes in white adipose depots, causing the activation of a process known as “browning”. Moreover, in vivo studies on adipose tissues show that T2, in addition to activating brown adipose tissue (BAT) thermogenesis, may further promote the browning of white adipose tissue (WAT), and affect adipocyte morphology, tissue vascularization, and the adipose inflammatory state in rats receiving a high-fat diet (HFD). In this review, we summarize the mechanism by which THs and thyroid hormone derivatives mediate adipose tissue activity and remodeling, thus providing noteworthy perspectives on their efficacy as therapeutic agents to counteract such morbidities as obesity, hypercholesterolemia, hypertriglyceridemia, and insulin resistance.

Body fat percentage and infarct size in patients with non-ST segment elevation myocardial infarction

“…Adipose tissue acts as an endocrine organ and performs important tasks for regulating body metabolism and homeostasis. Obesity causes aberrant remodeling and thus dysfunctional adipose tissue, which in turn results in the dysregulation of various molecules secreted by adipocytes (lipids, inflammatory cytokines, and hormones like leptin, adiponectin, resistin that regulate food intake, insulin sensitivity, and immune responses) [ 16 ]. These obesity-related alterations have deleterious effects on the cardiovascular system.…”

MHO or MUO? White adipose tissue remodeling

“…T3 directly binds to thyroid receptors (TRs) in AT, stimulating thermogenesis in brown fat 292 . Additionally, both T3 and 3,5‐diiodo‐L‐thyronine (T2) can facilitate the browning of WAT 293 . The specific response characteristics of GH signaling may vary between BAT and WAT.…”

“…292 Additionally, both T3 and 3,5-diiodo-L-thyronine (T2) can facilitate the browning of WAT. 293 The specific response characteristics of GH signaling may vary between BAT and WAT.…”

Interleukin-6: An Under-Appreciated Inducer of Thermogenic Adipocyte Differentiation

“…Gene networks controlled by Toll like receptors 3 and 4 (TLR3 and TLR4, respectively) as well as by nuclear factor kappa B (NFκB) become eventually actively transcribed, resulting in the excessive production of pro-inflammatory cytokines and reactive oxygen species [ 12 ]. Adipose tissue inflammation impedes insulin sensitivity, may cause β-cell destruction in the pancreatic islets, and may also exacerbate autoimmunity [ 13 , 14 ].…”