Dynamic Cross Talk Between Metabolic Organs in Obesity and Metabolic Diseases

EDITORIAL

Dynamic cross talk between metabolic organs in obesity and metabolic diseases

Experimental & Molecular Medicine (2016) 48, e214; doi:10.1038/emm.2015.119; published online 11 March 2016

uring evolution, living organisms have adapted to utilize Aimin Xu’s group (Hong Kong University) provides a Dvarious nutrient sources, including carbohydrates, comprehensive review of adipose tissue and its potential clinical lipids and proteins. In particular, carbohydrates and lipids implications. They have discussed the distinct characteristics of are the two major macromolecules serving as key components fat depots including white adipose tissue, brown adipose tissue of intracellular storage products for energy generation. and beige adipose tissue. There appear to be fat depot Importantly, anabolism and catabolism of these macro- differences in cellular composition and physiological property molecules are closely interwoven in organs involved in nutrient as a result of genetic or developmental events. Upon develop- regulation, including the brain, liver, adipose tissue, pancreas mental cues, hormonal changes, metabolic stresses and aging, and muscle. Among numerous organs and tissues, adipose distinct fat depots exhibit differences in their responses, as well tissues have key regulatory roles in survival, reproduction and as subsequent effects on energy metabolism, insulin sensitivity adaptation to nutritional stresses by way of their functioning as and thermogenesis. For instance, compared with subcutaneous a storage depot. For instance, adipose tissues actively expand in adipose tissue, visceral adipose tissue is prone to become response to excess energy intake and generate energy sources in chronically inflamed and insulin resistant in obesity. They also response to nutrient deficit, promptly engaging in the control provide insight into the potential role of adipose depot of systemic energy balance. In addition, adipose tissues specificity in mediating paradoxical phenotypes of two communicate with other metabolic organs through secreting populations—obese but metabolically healthy individuals and various adipokines, exerting multiple impacts on the regulation lean but metabolically unhealthy individuals. of systemic energy homeostasis. It is well established that the brain has an important role in Over the past few decades, the rate of obesity has grown the regulation of energy homeostasis by way of assessing rapidly around the world, imposing a high social burden in the current state of metabolism and energy homeostasis, terms of quality of life. Mounting evidence suggests that obesity and orchestrating modulation of both behavioral patterns is closely associated with the development of metabolic and peripheral metabolism. Various nutrients and hormones syndrome, including hyperlipidemia, hypertension, cardio- derived from adipose tissue, pancreas, stomach, intestines and vascular diseases, insulin resistance, hypercholesterolemia, liver convey information regarding the metabolic state to type 2 diabetes and even certain types of cancer. A hallmark multiple areas of the brain. After integrating peripheral of obesity is excessive expansion of body fat that is attributable metabolic, endocrine and neuronal signals, outflow pathways to chronic energy intake and sedentary lifestyle. Given the from the brain regulate food intake and energy expenditure. significant role of cross talk between adipose tissues and other Particularly, Min-Seon Kim's group (Asan Medical Center and metabolic organs related to the regulation of whole-body University of Ulsan) has focused on the critical role energy homeostasis, defining inter-organ metabolic commu- of the hypothalamus in the control of energy balance and nication involved in energy homeostasis would broaden the obesity. Given the fact that coordinated interactions between understanding of complex systems contributing to obesity. hypothalamus and peripheral metabolic organs engage in In this special issue, we will discuss recent findings on the governing whole-body energy homeostasis, defective signals cellular and molecular mechanisms in the cross talk of key from brain are closely linked to the detrimental effects of metabolic organs, including the brain, heart, liver, adipose obesity in relation to energy metabolism. tissue and pancreas, and their roles in the control of energy Recent findings have revised the concept of adipose tissues metabolism, as well as etiology of obesity. We also highlight the being a mere energy reservoir. Instead, adipose tissues are new findings from genetic and epigenetic studies on obesity endocrine organs that synthesize and secrete various signaling and its related diseases such as insulin resistance. molecules, the so-called adipokines. Accordingly, an increase Editorial

or a decrease in adiposity affects the circulating levels of variable interplay between the pancreas and other organs adipokines, leading to subsequent changes in systemic energy including, the brain, gut and liver, to coordinate whole-body homeostasis by modulating the energy metabolism in other energy metabolism. In addition, current therapeutic and organs. Similarly, recent studies on the heart reveal that heart is putative targets for the treatment of type 2 diabetes are another endocrine organ. Gary Sweeny's group (York Uni- discussed. versity) has highlighted the recent findings on cardiac remodel- Soo Heon Kwak and Kyong Soo Park (Seoul National ing mediated by cardiokines with multiple impacts on University Hospital) provide an overview of the current peripheral tissues. As a model system, they have focused on findings from genetic and epigenetic studies regarding type 2 myocardial inflammation in heart failure and underscored the diabetes. Despite type 2 diabetes being caused by multiple critical role of cardiokines in the modulation of cross talk factors, recent genetic association studies strongly suggest between heart and other tissues. that certain genetic variations are closely linked with the Liver is one of the primary sites of energy storage and is a incidence of type 2 diabetes. In addition to genetic factors, central organ in glucose and lipid metabolism. Excess environmental cues also contribute to the development of type energy from the diet is stored in the form of glycogen in the 2 diabetes by modulating epigenetic regulation, including DNA liver, and once glycogen depots are full any additional excess methylation, histone modification and non-coding RNAs. energy is piled in the form of lipid in adipose tissue. They discuss the plausible interactions between environmental Moreover, liver has an essential role in the complex factors, genetics and epigenetics to mediate pathogenesis of network of systemic energy metabolism by acting as the type 2 diabetes. major organ of glucose metabolism including glycogenesis, glycogenolysis, glycolysis and gluconeogenesis. Various Jae Bum Kim metabolites and hormones tightly regulate hepatic glucose Department of Biological Sciences, Institute of Molecular Biology metabolism by modulating elaborated transcriptional networks. and Genetics, National Creative Research Initiatives Center for Therefore, Seung-Hoi Koo's group (Korea University) discusses Adipose Tissue Remodeling, Seoul National University, the current understanding of hepatic energy homeostasis, Seoul, Korea particularly, with respect to key transcription factors and E-mail: [email protected] cofactors that are critical regulators of glucose and lipid metabolism. This work is licensed under a Creative Commons Insulin and glucagon are essential hormones to regulate Attribution-NonCommercial-ShareAlike 4.0 Inter- whole-body glucose and lipid metabolism, and both hormones national License. The images or other third party material in this are produced in the pancreas. Weiping Han's group (SBIC and article are included in the article’s Creative Commons license, A-STAR) provides an overview of pancreas development and unless indicated otherwise in the credit line; if the material is not its roles in glucose metabolism. They underscore the critical included under the Creative Commons license, users will need role of external cues, including gut hormones, nutrients, to obtain permission from the license holder to reproduce the cellular metabolites and ions in the development of the material. To view a copy of this license, visit http:// pancreas. They also discuss the molecular events underlying creativecommons.org/licenses/by-nc-sa/4.0/

Experimental & Molecular Medicine