Could burning fat start with a brite spark? Pharmacological and nutritional ways to promote thermogenesis

Abstract

There are two types of adipose tissue with distinct functions-white adipose tissue stores chemical energy as triglycerides, whereas brown adipose tissue consumes energy and releases heat (thermogenesis) in response to sympathetic nerve activity. In humans, treatments that promote greater brown adipose tissue deposition and/or activity would be highly beneficial in regimes aimed at reducing obesity. Adult humans have restricted populations of prototypical brown adipocytes in the neck and chest areas, but recent advances have established that adipocytes with similar properties, termed "brite" adipocytes, can be recruited in subcutaneous depots thought to be primarily white adipose tissue. These brite adipocytes express the protein machinery required for thermogenesis, but to assess brite adipocytes as viable therapeutic targets we need to understand how to promote conversion of white adipocytes to brite adipocytes and ways to increase optimal energy consumption and thermogenesis in these brite adipocytes. This can be accomplished by pharmacological and nutritional therapies to differing degrees, as reviewed in detail here.

Adrenoceptors in white, brown, and brite adipocytes

“…This does not discount the possibility of mirabegron being useful for obesity/diabetes treatment in the future, if β 3 ‐adrenoceptor expression could be increased in these patients. The notion of a dual therapy for activation of brown/brite adipocytes is gaining attention (Merlin et al, ). For example, the PPARγ agonist rosiglitazone promotes browning of white adipocytes, increases brite adipocyte β 3 ‐adrenoceptor expression, and thereby facilitates responsiveness to β 3 ‐adrenoceptor agonists (Merlin, Sato, Nowell, et al, ).…”

Mirabegron: potential off target effects and uses beyond the bladder

“…A recent discovery in the context of adipocyte biology is the discovery of “brite” ( br own within wh ite ) adipocytes (see Merlin et al . () for a review on brite adipocytes). Brite adipocytes are defined as brown‐like adipocytes located predominately in white adipose tissue depots.…”

“…Despite deriving from different precursor cells, both brite and brown adipocytes express UCP1. Importantly, brite adipocytes can be activated by environmental stimuli such as cold exposure and a range of pharmaceutical targets that include the β 3 ‐adrenoceptor (see Merlin et al, ). Brite adipocytes are found in adult humans in supraclavicular fat depots surrounded by white adipose tissues (Lidell et al, ), and their presence in humans is correlated with a metabolically healthy phenotype (Cypess et al, ), which makes them an attractive target for obesity‐related diseases.…”

“…One caveat is that white adipocytes must firstly be converted to a brite adipocyte before β 3 ‐adrenoceptors can activate them. Typically brite adipocytes are generated in vitro and in vivo from white adipocytes by the addition or administration of PPARγ ligands such as rosiglitazone (see Merlin et al, ). This allows increased UCP1 mRNA/protein that then can be activated by β 3 ‐adrenoceptor ligands (Li et al, ).…”

The early metabolomic response of adipose tissue during acute cold exposure in mice

“…Lipid metabolites in SWAT had a transitory response to cold exposure, with significant modulation of several lipid metabolites after 2–4 hours of cold exposure, followed by a return to thermoneutral levels at 6 hours. The study design and technologies applied have generated a data set of acute cold-induced metabolism in multiple tissues simultaneously that may guide further investigations of thermogenic regulation and support the development of anti-obesity therapeutics that target thermogenic mechanisms 4, 5, 18 .…”