Abstract
Presence of brown adipose tissue (BAT), characterized by the expression of the thermogenic uncoupling protein 1 (UCP1), has recently been described in adult humans. UCP1 is expressed in classical brown adipocytes, as well as in “beige cells” in white adipose tissue (WAT). The thermogenic activity of BAT is mainly controlled by the sympathetic nervous system. Endocrine factors, such as fibroblast growth factor 21 (FGF21) and bone morphogenic protein factor-9 (BMP-9), predominantly produced in the liver, were shown to lead to activation of BAT thermogenesis, as well as to “browning” of WAT. This was also observed in response to irisin, a hormone secreted by skeletal muscles. Different approaches were used to delineate the impact of UCP1 on insulin sensitivity. When studied under thermoneutral conditions, UCP1 knockout mice exhibited markedly increased metabolic efficiency due to impaired thermogenesis. The impact of UCP1 deletion on insulin sensitivity in these mice was not reported. Conversely, several studies in both rodents and humans have shown that BAT activation (by cold exposure, β3-agonist treatment, transplantation and others) improves glucose tolerance and insulin sensitivity. Interestingly, similar results were obtained by adipose tissue-specific overexpression of PR-domain-containing 16 (PRDM16) or BMP4 in mice. The mediators of such beneficial effects seem to include FGF21, interleukin-6, BMP8B and prostaglandin D2 synthase. Interestingly, some of these molecules can be secreted by BAT itself, indicating the occurrence of autocrine effects. Stimulation of BAT activity and/or recruitment of UCP1-positive cells are therefore relevant targets for the treatment of obesity/type 2 diabetes in humans.
Highlights
Obesity, well known to be associated with a number of comorbidities, including insulin resistance and type 2 diabetes, has become a major public health problem in recent decades, and has reached epidemic proportions, in high-income countries, and in most middle-income societies
It is defined as an accumulation of adipose tissue that is of sufficient magnitude to impair health (WHO, 2014)
Insulin resistance is present even in simple obesity, without hyperglycemia, indicating a fundamental abnormality of insulin signaling in states of excess adipose tissue mass
Summary
Well known to be associated with a number of comorbidities, including insulin resistance and type 2 diabetes, has become a major public health problem in recent decades, and has reached epidemic proportions, in high-income countries, and in most middle-income societies. It is defined as an accumulation of adipose tissue that is of sufficient magnitude to impair health (WHO, 2014). Excess weight is usually defined by the body mass index or BMI. Insulin resistance is present even in simple obesity, without hyperglycemia, indicating a fundamental abnormality of insulin signaling in states of excess adipose tissue mass. According to the World Health Organization, 347 millions of people are diabetic in the world, and it is predicted that in 2030, diabetes will be the 7th cause of death considering the worldwide population (WHO, 2014)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
