ABSTRACT
The regulation of energy balance involves an intricate interplay between neural mechanisms that respond to internal and external cues of energy demand and food availability. Compelling data have implicated the neurotransmitter dopamine as an important part of body weight regulation. However, the precise mechanisms through which dopamine regulates energy homeostasis remain poorly understood. Here, we investigate mechanisms through which dopamine modulates energy storage. We showed that dopamine signaling regulates fat reservoirs in Caenorhabditis elegans. We found that the fat reducing effects of dopamine were dependent on dopaminergic receptors and a set of fat oxidation enzymes. Our findings reveal an ancient role for dopaminergic regulation of fat and suggest that dopamine signaling elicits this outcome through cascades that ultimately mobilize peripheral fat depots.
Subject(s)
Caenorhabditis elegans/metabolism , Dopamine/metabolism , Fats/metabolism , Signal Transduction , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Dopamine/pharmacology , Dopamine Agents/metabolism , Dopamine Agents/pharmacology , Energy Metabolism/drug effects , Gene Expression , Homeostasis/drug effects , Lipid Metabolism/drug effects , Microscopy, Fluorescence , Mutation , Oxidation-Reduction/drug effects , RNA Interference , Receptors, Dopamine/genetics , Receptors, Dopamine/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Serotonin/pharmacology , Serotonin Receptor Agonists/pharmacology , Time FactorsABSTRACT
OBJECTIVE: The aim of this study was to examine the association between polymorphisms (SNP) in the tryptophan hydroxylase-2 (TPH2) gene and late-onset depression (LOD) in the Brazilian population. METHODS: We genotyped 8 tag SNPs in the TPH2 gene in 84 outpatients with LOD and 79 individuals belonging to the comparison group to investigate an association between the TPH2 gene and LOD. RESULTS: Our findings suggested an association between tag SNP rs4565946 heterozygous C/T (p = 0.034; χ2 = 6.7; df = 2) and decreased risk of LOD. The tag SNP rs11179000 ancestral homozygous A/A (p = 0.025; χ2 = 7.3; df = 2) and increase risk of LOD and allelic association of ancestral allele A and increase risk of LOD was demonstrated (p = 0.005; χ2 = 7.8; df = 1). CONCLUSION: We found the statistically significant association between two tag SNPs and LOD. Our results support the hypothesis that the TPH2 gene is associated with LOD.
Subject(s)
Depression/genetics , Tryptophan Hydroxylase/genetics , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Depression/diagnosis , Female , Genotype , Humans , Male , Polymorphism, Single Nucleotide/geneticsABSTRACT
BACKGROUND: DARPP-32 is a neuronal protein that plays a central role in dopaminergic neurotransmission. Although DARPP-32 may contribute to the pathogenesis of several human malignancies, its expression has never been investigated in oral premalignant and malignant lesions. MATERIALS AND METHODS: DARPP-32 expression was examined using immunohistochemistry in 14 normal oral mucosa, 5 normal lower lip mucosa, 41 oral leukoplakia (OL), 30 oral squamous cell carcinoma (OSCC) and 20 lower lip squamous cell carcinoma (LLSCC) specimens. Differences of its expression between groups were analyzed. RESULTS: OSCC and OL with moderate or severe dysplasia showed lower DARPP-32 expression in relation to normal oral mucosa. LLSCC showed lower DARPP-32 expression than normal lower lip mucosa and OSSC. CONCLUSION: The decreased expression of DARPP-32 in oral premalignant and malignant lesions suggests a tumor suppressor role for this protein in the tumorigenesis of these lesions.
