Brown adipose tissue (BAT) is a heat-producing organ that plays an important role in maintenance of energy homeostasis. The purpose of this study was to test a novel method for stimulating BAT thermogenesis in rats. Application of electrical field stimulation to the dorsal surface of interscapular BAT caused a substantial rise in tissue temperature without affecting rectal temperature. The electrical stimulation failed to raise BAT temperature on the 2nd day after surgical sympathetic denervation. This is unlikely to be due to loss of thermogenic capacity, since neither UCP1 contents nor norepinephrine-induced thermogenesis were diminished 2 days after the denervation. A pharmacological experiment revealed that the BAT thermogenesis induced after electrical stimulation is mediated through β-adrenoceptors. The present study demonstrates that electrical stimulation applied to the dorsal surface of BAT is able to activate thermogenesis of BAT through mediation of norepinephrine released from sympathetic nerves. Our findings may provide a basis for developing a novel therapeutic procedure for obesity and related disorders.
MicroRNAs (miRNAs) are endogenous small RNAs (length, 18-ss23 nucleotides) that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various diseases. In the present study, we explored cell- or tissue-specific miRNAs and assessed the applicability of miRNA profiling for identifying biomarkers of tissue injuries. miRNA analyses in various human and rat tissues identified several candidate miRNAs with possible tissue-specific expression, some of which have already been reported. In the present study, we focused on pancreas-specific miRNAs, miR-216a and miR-216b. Laser microdissection revealed that miR-216a and 216b were predominantly expressed in acinar cells of the pancreas as compared to Langerhans' islet. Plasma concentrations of miR-216a and miR-216b considerably increased in a rat model of L-arginineinduced acute pancreatitis. The current results have confirmed that miRNA expression profiling in various cells is useful for providing biomarkers for cell- or tissue-specific injuries.
We have reported that in ganglioside GM3-deficient (GM3-/-) mice, spontaneous alternation behavior assessed by a Y-maze task was significantly lower, and total arm entries were significantly higher than in wild-type mice. The objective of the present study was to examine the role of nicotinic acetylcholine receptor (nAChR) signaling in impairment of spontaneous alternation behavior of GM3-/- mice. Nicotine treatment (0.3, 1.0 mg/kg, s.c.) dose dependently improved the spontaneous alternation deficit without affecting total arm entries in GM3-/- mice. The nicotine-induced (1.0 mg/kg, s.c.) improvement was significantly abolished by the nAChR antagonist mecamylamine (1.0 mg/kg, i.p.). The α4β2 nAChR antagonist dihydro-β-erythroidine (2.5, 10.0 mg/kg, i.p.) dose dependently counteracted the nicotine-induced improvement of spontaneous alternation in GM3-/- mice, whereas the α7 nAChR antagonist methyllycaconitine (2.5, 10.0 mg/kg, i.p.) did not. In addition, the α4β2 nAChR agonist RJR-2403 (5.0, 10.0 mg/kg, s.c.) dose dependently and significantly improved the spontaneous alternation deficit, whereas the α7 nAChR agonist PNU120596 (0.3, 1.0, 3.0 mg/kg, i.p.) did not. These findings revealed that nicotine improved spontaneous alternation behavior of GM3-/- mice via the activation of α4β2, but not α7, nAChR. Thus, the ganglioside GM3 might be responsible for α4β2 nAChR signaling in the spontaneous alternation behavior.
Constant light conditions (LL) carry a risk of disrupting the biological clock of developing animals. Our purpose in this study was to investigate what disorders occur in animals receiving an LL stress during the late embryonic and suckling periods as compared with animals housed in dark-light (14 h-10 h) conditions (DL). In addition, we examined ameliorating effects against the disorder by the oral administration of lutein as an antioxidant. LL caused hypertrophy of the spleen and induced a higher expression of serotonin transporter (5HTT) in the corpus striatum and hippocampus in 15-day-old pups. In 9-week-old offspring, LL caused abnormal behavior in the elevated plus-maze test. The expression levels of 5HTT in the brain of the LL group changed to lower than those in DL group. The oral administration of lutein lessened the abnormality in behavior and 5HTT expression in the hippocampus to a certain degree although the expression levels of 5HTT in the corpus striatum were not altered by lutein diet. LL also induced disorders in the maternal brain with lower expression levels of 5HTT and neuregulin 1. These results indicate that LL during the perinatal periods may induce some neuronal abnormalities in both offspring and mothers that may be partially ameliorated by dietary lutein as an antioxidant.
Toll-like receptors (TLRs) play a critical role in innate immunity by recognizing pathogen-associated molecular patterns. Various environmental materials including lipids may affect TLR signaling and modulate innate immune responses. We previously reported that 10-hydroxy-trans-2-decenoic acid (10H2DA) inhibits lipopolysaccharide (LPS)-induced interleukin (IL)-6 and nitric oxide (NO) production via inhibiting NF-κB activation. In this study, we investigated the effect of 10-hydroxydecanoic acid (10HDA), a saturated fatty acid of 10H2DA, on LPS-induced cytokines/chemokines and NO production. 10HDA inhibited LPS-induced NO production, but not tumor necrosis factor-α or IL-6 production. LPS-induced activation of interferon (IFN)-stimulated response element, but not NF-κB, was inhibited by 10HDA. Phosphorylation of STAT1 and STAT2 was not affected, but IFN-regulatory factor (IRF)-1 production was significantly reduced by 10HDA. The LPS-induced increase of IRF-1 mRNA, however, was not affected by 10HDA. We found that IRF-1 mRNA level in the polysomal fraction was significantly decreased by 10HDA. Further, LPS-induced phosphorylation of Akt and 4E-BP1, which control mRNA translation, was markedly decreased. These results suggest that 10HDA inhibited LPS-induced NO production through inhibiting IRF-1 translation. These findings elucidate a novel mechanism for anti-inflammatory activity of medium-chain fatty acid 10HDA.