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Prolonged inorganic arsenic exposure via drinking water impairs brown adipose tissue function in mice. 2019

Zhuo Zuo, and Zhiyuan Liu, and Tianchang Gao, and Yuanyuan Yin, and Zhendi Wang, and Yongyong Hou, and Jingqi Fu, and Shengnan Liu, and Huihui Wang, and Yuanyuan Xu, and Jingbo Pi
Program of Environmental Toxicology, School of Public Health, China Medical University, No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.

Although epidemiologic studies show an association between long-term environmental inorganic arsenic (iAs) exposure and various disorders of glucose and lipid metabolism, the mechanisms of these ailments remain unclear. While white adipose tissue (WAT) essentially acts as a storage tissue for energy and is key to energy homeostasis, brown adipose tissue (BAT) consumes excess energy via uncoupling protein 1-mediated non-shivering thermogenesis in mitochondria and helps maintain the steady state of glucose and lipid metabolism. Our previous in vitro work found that iAs may inhibit adipogenesis and glucose uptake in adipocytes, leading us to hypothesize that chronic exposure to iAs in vivo may also affect the development and function of BAT, which plays a part in iAs-induced metabolic disorders. Thus, adult C57BL/6J female mice were provided drinking water containing 5 or 20 ppm of inorganic arsenicals (iAs3+ and iAs5+) for 17 weeks and control mice were given unaltered water. In these mice, iAs exposure induced cold intolerance and lipid accretion in BAT. In addition, iAs exposure impaired expression of various genes related to thermogenesis, mitochondrial function, adipocyte differentiation, as well as lipolysis in BAT of the exposed mice. These findings suggest a novel toxicity of iAs in BAT occurring via induction of BAT malfunction and impairment of thermogenesis. This novel toxicological linkage helps explain the mechanisms linking iAs exposure to increased risk of disorders of glucose and lipid metabolism.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D002001 Adipose Tissue, Brown A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids. Brown Fat,Hibernating Gland,Brown Adipose Tissue,Fat, Brown,Tissue, Brown Adipose
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D005260 Female Females
D000071256 Uncoupling Protein 1 A mitochondrial uncoupling protein that is expressed in BROWN ADIPOSE TISSUE. It is critical for NONSHIVERING THERMOGENESIS to prevent heat loss in NEONATES. BAT Uncoupling Protein,Brown Adipose Tissue Uncoupling Protein,Mitochondrial Brown Fat Uncoupling Protein 1,Mitochondrial Uncoupling Protein,SLC25A7 Protein,Solute Carrier Family 25 Member 7,Thermogenin,UCP1 Protein,Uncoupling Protein 1a,Uncoupling Protein, Mitochondrial Membrane,Uncoupling Protein, BAT,Uncoupling Protein, Mitochondrial
D000074341 Dietary Exposure The exposure to potentially harmful factors such as trace heavy metals, chemicals, radiation, or toxins due to FOOD CONTAMINATION including DRINKING WATER contamination. Exposure, Dietary
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001151 Arsenic A shiny gray element with atomic symbol As, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), arsenic and certain arsenic compounds have been listed as known carcinogens. (From Merck Index, 11th ed) Arsenic-75,Arsenic 75
D014874 Water Pollutants, Chemical Chemical compounds which pollute the water of rivers, streams, lakes, the sea, reservoirs, or other bodies of water. Chemical Water Pollutants,Landfill Leachate,Leachate, Landfill,Pollutants, Chemical Water

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