Chronic arsenic exposure impairs adaptive thermogenesis in male C57BL/6J mice. 2020

Felicia Castriota, and Peter-James H Zushin, and Sylvia S Sanchez, and Rachael V Phillips, and Alan Hubbard, and Andreas Stahl, and Martyn T Smith, and Jen-Chywan Wang, and Michele A La Merrill
Superfund Research Program, University of California, Berkeley, California.

The global prevalence of type 2 diabetes (T2D) has doubled since 1980. Human epidemiological studies support arsenic exposure as a risk factor for T2D, although the precise mechanism is unclear. We hypothesized that chronic arsenic ingestion alters glucose homeostasis by impairing adaptive thermogenesis, i.e., body heat production in cold environments. Arsenic is a pervasive environmental contaminant, with more than 200 million people worldwide currently exposed to arsenic-contaminated drinking water. Male C57BL/6J mice exposed to sodium arsenite in drinking water at 300 μg/L for 9 wk experienced significantly decreased metabolic heat production when acclimated to chronic cold tolerance testing, as evidenced by indirect calorimetry, despite no change in physical activity. Arsenic exposure increased total fat mass and subcutaneous inguinal white adipose tissue (iWAT) mass. RNA sequencing analysis of iWAT indicated that arsenic dysregulated mitochondrial processes, including fatty acid metabolism. Western blotting in WAT confirmed that arsenic significantly decreased TOMM20, a correlate of mitochondrial abundance; PGC1A, a master regulator of mitochondrial biogenesis; and, CPT1B, the rate-limiting step of fatty acid oxidation (FAO). Our findings show that chronic arsenic exposure impacts the mitochondrial proteins of thermogenic tissues involved in energy expenditure and substrate regulation, providing novel mechanistic evidence for arsenic's role in T2D development.

UI MeSH Term Description Entries
D008297 Male Males
D008689 Methacrylates Acrylic acids or acrylates which are substituted in the C-2 position with a methyl group. Methacrylate
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
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
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
D000071248 Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha A transcriptional co-activator for NUCLEAR RECEPTORS. It is characterized by an N-terminal LxxLL sequence, a region that interacts with PPAR GAMMA, and a C-terminal RNA RECOGNITION MOTIF. It increases expression of MITOCHONDRIAL UNCOUPLING PROTEIN to regulate genes involved in metabolic reprogramming in response to dietary restriction and the integration of CIRCADIAN RHYTHMS with ENERGY METABOLISM. PGC-1-alpha Protein,PPARGC-1-alpha Protein,PPARGC1a Protein,PGC 1 alpha Protein,PPARGC 1 alpha Protein,Peroxisome Proliferator Activated Receptor Gamma Coactivator 1 alpha
D000090622 Mitochondrial Precursor Protein Import Complex Proteins Multiprotein complexes that mediate import and sorting of mitochondrial preproteins into one of the four mitochondrial subcompartments: the outer membrane, the intermembrane space, the inner membrane, and the matrix. Mitochondrial protein import machinery includes translocase of the outer membrane (TOM) complex, translocases of the inner membrane (TIM) complex, beta‐barrel pathway complex, the mitochondrial intermembrane space import and assembly (MIA) pathway complex, carrier proteins of the inner membrane and the TIM23 complex and sorting and assembly machinery (SAM) complex. MIA Complex,MIM Complex,Mitochondrial Import Complex,Mitochondrial Intermembrane Space Import and Assembly Complex,Mitochondrial Precursor Protein Import Machinery Proteins,Mitochondrial Preprotein Translocases,Mitochondrial Protein Import Machinery Proteins,SAM Complex,Sorting and Assembly Machinery Complex,TIM Complex,TIM23 Complex,TIMM Complex,TOM Channel,TOM Complex,TOM Translocase,TOMM Complex,TOMM Machinery,Translocase Outer Mitochondrial Membrane,Translocase of the Inner Membrane Complex,Translocase of the Inner Mitochondrial Membrane Complex,Translocase of the Outer Membrane Complex,Translocases of the Inner Membrane 23 Complex,Translocases of the Inner Membrane Complex,Import Complex, Mitochondrial,Preprotein Translocases, Mitochondrial,Translocase, TOM,Translocases, Mitochondrial Preprotein
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
D012833 Siloxanes Silicon polymers that contain alternate silicon and oxygen atoms in linear or cyclic molecular structures. Polysiloxane,Polysiloxanes,Siloxane

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