Omega-3 Fats Stimulate Metabolism of Brown Fat

Brown fat, or more precisely Brown Adipose Tissue (BAT), has long been a target for increasing fat loss and reducing the risk of type-II diabetes. BAT promotes heat production (thermogenesis) in mammals, which is essential for small mammal survival cold environments (and for arousal in hibernators).

Brown adipocytes in BAT are packed with mitochondria that contain uncoupling protein-1 (UCP1). UCP1, when activated, short circuits the electrochemical gradient that drives ATP synthesis and thereby stimulates respiratory chain activity. Heat is generated from the combustion of available substrates and is distributed to the rest of the body through the circulation. [Harms and Seale (2013); Brown and beige fat: development, function and therapeutic potential. Nature Medicine; 19:1252–1263]

The infamous Dan Duchaine (aka, The Steroid Guru) is credited with bring DNP (2,4-Dinitrophenol) and then usnic acid to the bodybuilding world. Both of these substances increase UCP1 expression, increasing metabolism dramatically, and causing fat loss. But DNP can be frequently fatal and usnic acid is highly liver toxic for most people.

This new research (as well as some previous studies) demonstrate the omega-3 fats can activate UCP1 without the harmful side effects of the drugs once commonly used in bodybuilding. It may be slower in its action, but omega-3 fats have so many other benefits that it is more than worth the slower results.

Omega-3 fatty acids stimulate brown adipose tissue metabolism

21 November 2016; Universidad de Barcelona

Omega-3 fatty acids are able to stimulate the activation of brown and beige adipose tissues, a discovery that would promote the development of new therapies for obesity and other metabolism diseases, according to a research study published in the journal Nature Communications under the supervision of Professor Francesc Villarroya, from the Department of Biochemistry and Molecular Biomedicine and the Biomedical Research Center Red-Fisiopatología de la Obesidad y Nutrición (CIBEROBN) of the Institute of Health Carlos III.

In the new study, carried out in laboratory animal models, the research team noticed that Omega-3 fatty acids (n-3 PUFAS) stimulate the activation of brown and beige adipose tissue through a specific receptor (GPR120), which enables the release of the hormone FGF21 (21 fibroblast growth factor). This hormone, built by the adipocyte, is a molecule that regulates lipid glucose and metabolism and therefore, it is an effective target for the action mechanism of Omega-3.

“This discovery has implications in the understanding of the positive effects of n-3 PUFAS on the control of metabolic diseases and other aspects regarding the treatment for obesity and type 2 diabetes”, says Professor Francesc Villarroya, member of the Institute of Biomedicine of the University of Barcelona (IBUB) and head of the Research Group in Genetics and Molecular Biology of Mitochondrial Proteins and Associated Diseases.

Protection key factors to tackle obesity

The study shows that Omega-3 fatty acids enable the adaptive thermogenesis in mammals’ brown adipose tissue, an essential mechanism for the adaption of the organism to cold environments. With rodents, it has been proved that the brown adipose tissue is able to create warmth and protect from obesity through the activation of energy expenditure.

According to the conclusions of the article published in Nature Communications, the specific receptor GPR120 for the Omega poli-unsaturated fatty acids enables the activation of brown adipose tissue, which is linked –in several scientific studies- to protection from obesity and metabolic diseases such as diabetes or dyslipemia (alterations in lipid metabolism).

The main function of brown adipose tissue is to burn calories and to make physical warmth out of fat (thermogenesis). However, a recent study by this research team has defined that brown adipose tissue also acts as an endocrine organ and can secrete factors that activate fat and carbohydrates metabolism. The most known factors up to now are FGF21, neuregulin 4 and interleukin-6, among other molecules of biological interest.

According to Francesc Villarroya, “these molecules, released by the adipose tissue (brown adipocytes or batokines) have positive metabolic effects. For this reason, they could be used in new therapies for obesity and related metabolic diseases”.

Citation:

Tania Quesada-López, Rubén Cereijo, Jean-Valery Turatsinze, Anna Planavila, Montserrat Cairó, Aleix Gavaldà-Navarro, Marion Peyrou, Ricardo Moure, Roser Iglesias, Marta Giralt, Decio L. Eizirik & Francesc Villarroya. The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes. Nature Communications (2017, Nov); Article number: 13479 (2016).
DOI: 10.1038/ncomms13479

Here is the abstract and introduction to the article, which is Open Access.

Abstract

The thermogenic activity of brown adipose tissue (BAT) and browning of white adipose tissue are important components of energy expenditure. Here we show that GPR120, a receptor for polyunsaturated fatty acids, promotes brown fat activation. Using RNA-seq to analyse mouse BAT transcriptome, we find that the gene encoding GPR120 is induced by thermogenic activation. We further show that GPR120 activation induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired cold-induced browning. Omega-3 polyunsaturated fatty acids induce brown and beige adipocyte differentiation and thermogenic activation, and these effects require GPR120. GPR120 activation induces the release of fibroblast growth factor-21 (FGF21) by brown and beige adipocytes, and increases blood FGF21 levels. The effects of GPR120 activation on BAT activation and browning are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 activates brown fat via a mechanism that involves induction of FGF21.

Introduction

Brown adipose tissue (BAT) is the main site of non-shivering thermogenesis in mammals. It confers a unique mechanism for energy expenditure and heat production in response to cold and provides a protective mechanism against excessive body weight accumulation in response to overfeeding [1,2].The interest in brown fat activity as a mechanism of protection against the obesity and metabolic diseases has been renewed by the recent recognition that adult humans possess active BAT, and its activity is negatively associated with obesity and type II diabetes [3]. Many aspects of the molecular mechanisms underlying the function of BAT are known, but we do not comprehensively understand how BAT activity is controlled and integrated with whole organism metabolism to ensure that metabolic substrates are burned and heat is provided. Recent studies unravelled an additional BAT-related means to control energy expenditure, wherein white adipose tissue (WAT) has the capacity to acquire BAT-like properties via the so-called ‘browning’ process. During this process, sustained thermogenic activation leads to the appearance of the so-called beige or brite adipocytes in WAT depots, which, like classical brown adipocytes, express uncoupling protein-1 (UCP1) and perform uncoupled mitochondrial respiration [4,5]. Several lines of evidence suggest that the browning process is especially relevant in controlling whole-body energy balance [4]. This may reflect its high inducibility in response to environmental factors and the ability of beige cells to use additional, non-UCP1-mediated energy expending mechanisms [6].

Studies aimed at assessing how BAT responds to cold can improve our understanding of the processes that mediate BAT activation. Transcriptomic profiling of BAT from cold-exposed mice can provide a snapshot of how BAT responds to the thermogenic activation and may offer an unbiased look at novel BAT activity-related actors. Recently, RNA sequencing (RNA-seq) has emerged as the best tool for transcriptomic studies, as it does not require a priori knowledge of targets, and shows both high reproducibility and a low frequency of false positives [7,8,9]. Moreover, RNA-seq can identify 25–75% more genes than complementary DNA (cDNA) microarrays, and it allows assessment of both whole genes and splice variants [10,11].

Here we used RNA-seq to analyse the responsiveness of BAT to the cold-induced thermogenic activation. Departing from these data set, we identified a novel pathway through which thermogenic activation of BAT and the browning of WAT occur via the activation of GPR120 (FFAR4). GPR120 is a G-protein-coupled receptor that binds unsaturated long-chain fatty acids and their derivatives [12]. GPR120 is known to contribute to mediating the anti-inflammatory actions of polyunsaturated fatty acids (PUFAs) and in protecting against obesity and type II diabetes [13,14]. Here we identify a novel pathway of thermogenic regulation through that PUFA-mediated GPR120 activation induces BAT activity and WAT browning via the hormonal factor fibroblast growth factor-21 (FGF21).