1. Investigación

The incidence of obesity and its related disorders has increased dramatically in recent years and has become a pandemic. Adipose tissue is a crucial regulator of these diseases due to its endocrine capacity. Thus, understanding adipose tissue metabolism is essential to finding new effective therapeutic approaches. The “omic” revolution has identified new concepts about the complexity of the signaling pathways involved in the pathophysiology of adipose tissue-associated disorders. Specifically, advances in transcriptomics have allowed its application in clinical practice and primary or secondary prevention. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of adipose tissue since they can modulate gene expression at the epigenetic, transcriptional, and post-transcriptional levels. They interact with DNA, RNA, protein complexes, other noncoding RNAs, and microRNAs to regulate a wide range of physiological and pathological processes. Here, we review the emerging field of lncRNAs, including how they regulate adipose tissue biology, and discuss circulating lncRNAs, which may represent a turning point in the diagnosis and treatment of adipose tissue-associated disorders. We also highlight potential biomarkers of obesity and diabetes that could be considered as therapeutic targets.

Brown adipose tissue (BAT) dissipates energy to produce heat. Thus, it has the potential to regulate body temperature by thermogenesis. For the last decade, BAT has been in the spotlight due to its rediscovery in adult humans. This is evidenced by over a hundred clinical trials that are currently registered to target BAT as a therapeutic tool in the treatment of metabolic diseases, such as obesity or diabetes. The goal of most of these trials is to activate the BAT thermogenic program via several approaches such as adrenergic stimulation, natriuretic peptides, retinoids, capsinoids, thyroid hormones, or glucocorticoids. However, the impact of BAT activation on total body energy consumption and the potential effect on weight loss is still limited. Other studies have focused on increasing the mass of thermogenic BAT. This can be relevant in obesity, where the activity and abundance of BAT have been shown to be drastically reduced. The aim of this review is to describe pathological processes associated with obesity that may influence the correct differentiation of BAT, such as catecholamine resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. This will shed light on the thermogenic potential of BAT as a therapeutic approach to target obesity-induced metabolic diseases.

The rediscovery of brown adipose tissue (BAT) in humans and its capacity to oxidize fat and dissipate energy as heat has put the spotlight on its potential as a therapeutic target in the treatment of several metabolic conditions including obesity and diabetes. To date the measurement of bioenergetics parameters has required the use of cultured cells or extracted mitochondria with the corresponding loss of information in the tissue context. Herein, we present a method to quantify mitochondrial bioenergetics directly in BAT. Based on XF Seahorse Technology, we assessed the appropriate weight of the explants, the exact concentration of each inhibitor in the reaction, and the specific incubation time to optimize bioenergetics measurements. Our results show that BAT basal oxygen consumption is mostly due to proton leak. In addition, BAT presents higher basal oxygen consumption than white adipose tissue and a positive response to b-adrenergic stimulation. Considering the whole tissue and not just subcellular populations is a direct approach that provides a realistic view of physiological respiration. In addition, it can be adapted to analyze the effect of potential activators of thermogenesis, or to assess the use of fatty acids or glucose as a source of energy.

Obesity is associated with severe metabolic diseases such as type 2 diabetes, insulin resistance, cardiovascular disease and some forms of cancer. The pathophysiology of obesity-induced metabolic diseases has been strongly related to white adipose tissue (WAT) dysfunction through several mechanisms such as fibrosis, apoptosis, inflammation, ER and oxidative stress. However, little is known of whether these processes are also present in brown adipose tissue (BAT) during obesity, and the potential consequences on mitochondrial activity. Here we characterized the BAT of obese and hyperglycemic mice treated with a high-fat diet (HFD) for 20 weeks. The hypertrophic BAT from obese mice showed no signs of fibrosis nor apoptosis, but higher levels of inflammation, ER stress, ROS generation and antioxidant enzyme activity than the lean counterparts. The response was attenuated compared with obesity-induced WAT derangements, which suggests that BAT is more resistant to the obesity-induced insult. In fact, mitochondrial respiration in BAT from obese mice was enhanced, with a 2-fold increase in basal oxygen consumption, through the upregulation of complex III of the electron transport chain and UCP1. Altogether, our results show that obesity is accompanied by an increase in BAT mitochondrial activity, inflammation and oxidative damage.