An update on brown adipose tissue and obesity intervention: Function, regulation and therapeutic implications

Abstract

Overweight and obesity have become a world-wide problem. However, effective intervention approaches are limited. Brown adipose tissue, which helps maintain body temperature and contributes to thermogenesis, is dependent on uncoupling protein1. Over the last decade, an in-creasing number of studies have found that activating brown adipose tissue and browning of white adipose tissue can protect against obesity and obesity-related metabolic disease. Brown adipose tissue has gradually become an appealing therapeutic target for the prevention and re-versal of obesity. However, some important issues remain unresolved. It is not certain whether increasing brown adipose tissue activity is the cause or effect of body weight loss or what the risks might be for sympathetic nervous system-dependent non-shivering thermogenesis. In this review, we comprehensively summarize approaches to activating brown adipose tissue and/or browning white adipose tissue, such as cold exposure, exercise, and small-molecule treatment. We highlight the functional mechanisms of small-molecule treatment and brown adipose tissue transplantation using batokine, sympathetic nervous system and/or gut microbiome. Finally, we discuss the causality between body weight loss induced by bariatric surgery, exercise, and brown adipose tissue activity.

Designer Fat Cells: Adipogenic Differentiation of CRISPR-Cas9 Genome-Engineered Induced Pluripotent Stem Cells

“…Perhaps at an early timepoint of 7 days, PDiPSCs can likely be successfully differentiated into brown and white adipocytes, but the culture must be analyzed through day 14 to see apparent phenotypic differences in the outcomes we assessed. The three depots of adipose tissue – white, brown, and beige – are phenotypically and functionally distinct (Lidell et al ., 2014; Liu et al ., 2022; Soler-Vázquez et al ., 2018; Trayhurn, 2018), and the ability to engineer these distinct adipose tissues and individually knockout genes of interest can help us to understand potential therapeutic or harmful effects of different adipose subtypes. Previous groups have successfully generated brown-like ADMSCs using genome engineering techniques and the beneficial effects of transplantation of these cells into obese mice, including improved glucose tolerance, insulin sensitivity, and increased energy expenditure (Wang et al ., 2020).…”

MHO or MUO? White adipose tissue remodeling

“…White adipocytes are responsible for storing and releasing FFAs, whereas beige and brown adipocytes dissipate energy by generating heat 127 . White adipocytes store energy in the form of triglycerides, which are stored in lipid droplets that can occupy over 90% of the cell volume.…”

“…White adipocytes are responsible for storing and releasing FFAs, whereas beige and brown adipocytes dissipate energy by generating heat. 127 White adipocytes store energy in the form of triglycerides, which are stored in lipid droplets that can occupy over 90% of the cell volume. In comparison, beige and brown fat cells boast a wealth of mitochondria rich in cristae, exhibit the expression of uncoupling protein 1 (UCP1), and possess multilocular lipid droplets.…”

Bringing equine adipose tissue into focus

“…Most adult mammals have very low quantities of brown AT and indeed, this form has not been described at all in the adult horse. There is great interest in brown AT pharmacological activation as a novel therapeutic target in human obesity (Liu et al, 2022); further research into brown AT in horse may, therefore, be of interest.…”