Methylmercury (MeHg) is a well-known neurotoxicant; however, its role in metabolic diseases has been gaining wider attention. Chronic exposure to MeHg in human populations shows an association with diabetes mellitus and metabolic syndrome (MS). As the incidences of both obesity and MS are on the rise globally, it is important to understand the potential role of MeHg in the development of the disease. There is a dearth of information on dietary interactions between MeHg and lipids, which play an important role in developing MS. We have previously shown that MeHg increases food seeking behaviors, lipid levels, fat storage, and pro-adipogenic gene expression in C. elegans fed the standard OP50 Escherichia coli diet. However, we hypothesized that these metabolic changes could be prevented if the worms were fed a bacterial diet lower in lipid content. We tested whether C. elegans developed metabolic alterations in response to MeHg if they were fed two alternative E. coli strains (HT115 and HB101) that are known absorb significantly less lipids from their media. Additionally, to explore the effect of a high-lipid and high-cholesterol diet on MeHg-induced metabolic dysfunction, we supplemented the OP50 strain with twice the standard concentration of cholesterol in the nematode growth media. Wild-type worms fed either the HB101 or HT115 diet were more resistant to MeHg than the worms fed the OP50 diet, showing a significant right-hand shift in the dose–response survival curve. Worms fed the OP50 diet supplemented with cholesterol were more sensitive to MeHg, showing a significant left-hand shift in the dose–response survival curve. Changes in sensitivity to MeHg by differential diet were not due to altered MeHg intake in the worms as measured by inductively coupled mass spectrometry. Worms fed the low-fat diets showed protection from MeHg-induced metabolic changes, including decreased food consumption, lower triglyceride content, and lower fat storage than the worms fed either of the higher-fat diets. Oxidative stress is a common characteristic of both MeHg exposure and high-fat diets. Worms fed either OP50 or OP50 supplemented with cholesterol and treated with MeHg had significantly higher levels of reactive oxygen species, carbonylated proteins, and loss of glutathione than the worms fed the HT115 or HB101 low-lipid diets. Taken together, our data suggest a synergistic effect of MeHg and dietary lipid levels on MeHg toxicity and fat metabolism in C. elegans, which may affect the ability of MeHg to cause metabolic dysfunction.

Metabolic effects of methylmercury (MeHg) are gaining wider attention. We have previously shown that MeHg causes lipid dysregulation in Caenorhabditis elegans (C. elegans), leading to altered gene expression, increased triglyceride levels and lipid storage, and altered feeding behaviors. Transcriptional regulators, such as transcription factors and microRNAs (miRNAs), have been shown to regulate lipid storage, serum triglycerides, and adipogenic gene expression in human and rodent models of metabolic diseases. As we recently investigated adipogenic transcription factors induced by MeHg, we were, therefore, interested in whether MeHg may also regulate miRNA sequences to cause metabolic dysfunction. Lipid dysregulation, as measured by triglyceride levels, lipid storage sites, and feeding behaviors, was assessed in wild-type (N2) worms and in transgenic worms that either were sensitive to miRNA expression or were unable to process miRNAs. Worms that were sensitive to the miRNA expression were protected from MeHg-induced lipid dysregulation. In contrast, the mutant worms that were unable to process miRNAs had exacerbated MeHg-induced lipid dysregulation. Concurrent with differential lipid homeostasis, miRNA-expression mutants had altered MeHg-induced mitochondrial toxicity as compared to N2, with the miRNA-sensitive mutants showing mitochondrial protection and the miRNA-processing mutants showing increased mitotoxicity. Taken together, our data demonstrate that the expression of miRNAs is an important determinant in MeHg toxicity and MeHg-induced metabolic dysfunction in C. elegans.

An increase in the amount of long-chain fatty acids in liver glycolipid of rats subjected to a hyperbaric exposure and fast decompression has been reported (1). A similar observation was reported in the glycolipids of liver, kidney, and spleen from rats exposed to 20 atmosphere-absolute (ATA) of He-0, when animals were compared to those held at 1 ATA of He-0, (2). An attempt was made to correlate the alteration in the amount of fatty acids and the enzyme activity involved in fatty acid chain elongation and desaturation under hyperbaric exposure. This paper is a report on the enzyme activities associated with chain elongation and desaturation of palmitic acid in liver microsomes of rats exposed to 20 ATA of He-0,.Materials and methods. Simulated diving experiments were performed according to the procedure described by Bitter and Nielsen (3). Male Sprague-Dawley rats, with an average weight of 200 g, fed regular lab chow were subjected to a hyperbaric exposure of 20 ATA (He-0,) for 12 hr and subsequently to a 7-hr decompression schedule. Two control groups of animals each were held in ambient air and 1 ATA of He-0,.Following decompression, the animals were anesthetized with ether and bled. The livers were removed immediately, homoge-

Accumulation of monoglycosyl ceramide occurs in plasma and red blood cells as well as chain elongation of fatty acids in liver glycolipids from rats subjected to a hyperbaric environment (N2-02) and rapid decompression (1). Helium is more advantageous to use in diving than N2 and has been substituted for N2 in the breathing mixture in deep sea diving experiments. However, helium can affect cellular metabolism at both ambient and high pressures (2-7). This report presents the changes in sphingoglycolipids of liver, kidney, lung and spleen in rats exposed to a gas mixture of He-02 at 1 atmosphere-absolute (ATA) and 20 ATA. Materials and Methods.Adult male Sprague-Dawley rats (five animals per group) with an average weight of 300 g were placed in a chamber at 5 PM. The chamber was flushed with 100% oxygen to remove all the residual nitrogen and then flushed with 100% helium until an approximate 75-25% He-02 mixture was reached. This mixture was monitored by gas liquid chromatography. The pressure was increased with 100% helium at a rate of 0.5 ATA per min to 20 ATA. Animals were held at 20 ATA pressure until 7 AM the following morning.