The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Alan R. Saltiel - One of the best experts on this subject based on the ideXlab platform.
-
Adapting to obesity with Adipose Tissue inflammation
Nature Reviews Endocrinology, 2017Co-Authors: Shannon M. Reilly, Alan R. SaltielAbstract:Adipocytes have an important role in sensing and managing energy status Adipose Tissue responds to overnutrition by mounting an immune response; however, the initial inflammatory trigger in Adipose Tissue is unknown Inflammation induces insulin resistance through a variety of molecular mechanisms The maladaptive responses that occur in long-term obesity are a result of chronic inflammation, particularly catecholamine resistance Inflammatory pathways are intriguing therapeutic targets for metabolic disease; however, the clinical efficacy of drugs targeting these pathways has been disappointing Adipose Tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Here, Reilly and Saltiel review the cellular and molecular mechanisms of obesity-induced inflammation in Adipose Tissue and discuss potential therapeutic approaches. Adipose Tissue not only has an important role in the storage of excess nutrients but also senses nutrient status and regulates energy mobilization. An overall positive energy balance is associated with overnutrition and leads to excessive accumulation of fat in adipocytes. These cells respond by initiating an inflammatory response that, although maladaptive in the long run, might initially be a physiological response to the stresses obesity places on Adipose Tissue. In this Review, we characterize Adipose Tissue inflammation and review the current knowledge of what triggers obesity-associated inflammation in Adipose Tissue. We examine the connection between Adipose Tissue inflammation and the development of insulin resistance and catecholamine resistance and discuss the ensuing state of metabolic inflexibility. Finally, we review the current and potential new anti-inflammatory treatments for obesity-associated metabolic disease.
-
adapting to obesity with Adipose Tissue inflammation
Nature Reviews Endocrinology, 2017Co-Authors: Shannon M. Reilly, Alan R. SaltielAbstract:Adipose Tissue not only has an important role in the storage of excess nutrients but also senses nutrient status and regulates energy mobilization. An overall positive energy balance is associated with overnutrition and leads to excessive accumulation of fat in adipocytes. These cells respond by initiating an inflammatory response that, although maladaptive in the long run, might initially be a physiological response to the stresses obesity places on Adipose Tissue. In this Review, we characterize Adipose Tissue inflammation and review the current knowledge of what triggers obesity-associated inflammation in Adipose Tissue. We examine the connection between Adipose Tissue inflammation and the development of insulin resistance and catecholamine resistance and discuss the ensuing state of metabolic inflexibility. Finally, we review the current and potential new anti-inflammatory treatments for obesity-associated metabolic disease.
Rinke Stienstra - One of the best experts on this subject based on the ideXlab platform.
-
Adipose Tissue macrophages: going off track during obesity
Diabetologia, 2016Co-Authors: Lily Boutens, Rinke StienstraAbstract:Inflammation originating from the Adipose Tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes Adipose Tissue inflammation, this review is specifically focused on the contribution of macrophages that reside in Adipose Tissue in lean and obese conditions. Both conventional and Tissue-specific functions of Adipose Tissue macrophages (ATMs) in lean and obese Adipose Tissue are discussed and linked with metabolic and inflammatory changes that occur during the development of obesity. Furthermore, we will address various circulating and Adipose Tissue-derived triggers that may be involved in shaping the ATM phenotype and underlie ATM function in lean and obese conditions. Finally, we will highlight how these changes affect Adipose Tissue inflammation and may be targeted for therapeutic interventions to improve insulin sensitivity in obese individuals. Highlights • Macrophages play a significant role in regulating Adipose Tissue functioning during health and disease • In addition to conventional functions such as clearing cellular debris and participating in Tissue immune surveillance, lipid buffering is an important function of ATMs • Obesity-induced inflammation, characterised by an elevated number of proinflammatory macrophages in Adipose Tissue, has been suggested to contribute to systemic insulin resistance • Their origin, as well as a combination of peripheral changes and Adipose Tissue-derived stressors, probably contribute to ATM dysfunction and inflammatory traits during obesity • Identification of transcriptional differences between ATMs from lean vs obese Adipose Tissue at several key points during the development of obesity and insulin resistance may reveal upstream triggers, regulatory factors and intracellular pathways that shape ATM function • Targeting metabolic capacity rather than the inflammatory phenotype of ATMs may hold potential to restore ATM function and Adipose Tissue homeostasis in obese individuals
-
Adipose Tissue macrophages
Diabetologia, 2016Co-Authors: Lily Boutens, Rinke StienstraAbstract:Inflammation originating from the Adipose Tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes Adipose Tissue inflammation, this review is specifically focused on the contribution of macrophages that reside in Adipose Tissue in lean and obese conditions. Both conventional and Tissue-specific functions of Adipose Tissue macrophages (ATMs) in lean and obese Adipose Tissue are discussed and linked with metabolic and inflammatory changes that occur during the development of obesity. Furthermore, we will address various circulating and Adipose Tissue-derived triggers that may be involved in shaping the ATM phenotype and underlie ATM function in lean and obese conditions. Finally, we will highlight how these changes affect Adipose Tissue inflammation and may be targeted for therapeutic interventions to improve insulin sensitivity in obese individuals.(Table presented.)
Esben Søndergaard - One of the best experts on this subject based on the ideXlab platform.
-
Quantification of Adipose Tissue insulin sensitivity.
Journal of Investigative Medicine, 2016Co-Authors: Esben Søndergaard, Michael D. JensenAbstract:In metabolically healthy humans, Adipose Tissue is exquisitely sensitive to insulin. Similar to muscle and liver, Adipose Tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in Adipose Tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those Tissues. It has been hypothesized that insulin Adipose Tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of Adipose Tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine Adipose Tissue insulin sensitivity. We review the methods available to quantitate Adipose Tissue insulin sensitivity and will discuss their strengths and weaknesses.
-
Chronic adrenergic stimulation induces brown Adipose Tissue differentiation in visceral Adipose Tissue.
Diabetic Medicine, 2015Co-Authors: Esben Søndergaard, Lars C. Gormsen, Mette Høgh Christensen, Steen B. Pedersen, P Christiansen, Søren Nielsen, P. L. Poulsen, Niels JessenAbstract:Background Recruitment of brown Adipose Tissue is a promising strategy to treat obesity and Type 2 diabetes, but the physiological effects of a large amount of metabolically active brown Adipose Tissue in humans are unknown. Case report In the present paper, we report a case of massive brown Adipose Tissue infiltration of the visceral Adipose Tissue depot in a person with Type 2 diabetes with a catecholamine-secreting paraganglioma. The patient was evaluated with [18F]-fludeoxyglucose positron emission tomography/computed tomography on three occasions: pre-therapy, during α-blockade and postoperatively. During surgery, biopsies of visceral and subcutaneous Adipose Tissue were obtained and evaluated for brown Adipose Tissue. At diagnosis, brown Adipose Tissue glucose uptake, assessed by [18F]-fludeoxyglucose-positron emission tomography, was massively increased. [18F]-fludeoxyglucose uptake was confined to known locations for brown Adipose Tissue, with additional uptake in the visceral Adipose Tissue. As a result of increased thermogenesis, resting energy expenditure was doubled. After surgical removal of the tumour, antidiabetic medicine was no longer needed, despite an 8.2-kg weight gain. Conclusion These results show that human visceral Adipose Tissue holds an unprecedented potential for brown adipogenic differentiation; however, a detrimental effect on glucose metabolism persisted despite massive brown Adipose Tissue activity, with a doubling of resting energy expenditure.
S W Coppack - One of the best experts on this subject based on the ideXlab platform.
-
Adipose Tissue changes in obesity.
Biochemical Society transactions, 2005Co-Authors: S W CoppackAbstract:This review gives a broad description of some of the changes in Adipose Tissue seen in obesity. There are multiple changes in Adipose Tissue in obesity: histological, neural and vascular, relating to lipid and carbohydrate metabolism and to Adipose Tissue's endocrine functions. Some may originate from a simple physical expansion of cell size and number. It is unclear which are the most important either in terms of intermediary metabolism or of contributing to the co-morbidities of obesity. Important questions for the future include the reversibility of obesity-related changes and indeed whether the changes differ between depots and species. Recent studies examining physiological regulation within Adipose Tissue demonstrate it to be relatively unresponsive to changes in everyday life.
-
Integrative physiology of human Adipose Tissue
International Journal of Obesity, 2003Co-Authors: K N Frayn, F Karpe, B A Fielding, I A Macdonald, S W CoppackAbstract:Adipose Tissue is now recognised as a highly active metabolic and endocrine organ. Great strides have been made in uncovering the multiple functions of the adipocyte in cellular and molecular detail, but it is essential to remember that Adipose Tissue normally operates as a structured whole. Its functions are regulated by multiple external influences such as autonomic nervous system activity, the rate of blood flow and the delivery of a complex mix of substrates and hormones in the plasma. Attempting to understand how all these factors converge and regulate Adipose Tissue function is a prime example of integrative physiology. Adipose Tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose Tissue possesses the ability to a very large extent to modulate its own metabolic activities, including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other Tissues to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. This implies the existence of one (or more) signal(s) to the Adipose Tissue that reflects the body's energy status, and points once again to the need for an integrative view of Adipose Tissue function.
Alyssa H Hasty - One of the best experts on this subject based on the ideXlab platform.
-
Adipose Tissue recruitment of leukocytes
Current Opinion in Lipidology, 2010Co-Authors: Emily K Anderso, Dario A Gutierrez, Alyssa H HastyAbstract:Purpose of review In December of 2003, two seminal articles describing the presence of macrophages in obese Adipose Tissue were published. These Adipose Tissue macrophages (ATMs) are inflammatory and promote local and systemic insulin resistance. Due to the continuing rise in obesity around the world, understanding how these ATMs contribute to metabolic disorders is of much interest. Recent findings Chemokines have been extensively studied for their role in ATM recruitment. Deficiency or antagonism of chemokine receptors that interact with multiple chemokine ligands reduces ATM accumulation. ATMs are now defined as either classically (M1) or alternatively (M2) activated. Peroxisome proliferator-activated receptor activation and adiponectin promote an M2-polarized state resulting in improved insulin sensitivity. Finally, recent studies have provided evidence that T lymphocytes, natural killer T cells, mast cells, and B cells also enter Adipose Tissue and may interact with macrophages and adipocytes. Summary Literature published during the past year has shown that macrophage recruitment to Adipose Tissue is only one of the important mediators of obesity-related insulin resistance. The phenotype of ATMs and recruitment of other immune cells to the Adipose Tissue play key roles in the overall contribution of Adipose Tissue to systemic metabolic outcomes of obesity.
