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Although the importance of lipid homeostasis in neuronal function is undisputed, how they are regulated within neurons to support their unique function is an area of active study. NHR-49 is a nuclear hormone receptor functionally similar to PPARα, and a major lipid regulator in C. elegans. Although expressed in most tissues, little is known about its roles outside the intestine, the main metabolic organ of C. elegans. Here, using tissue- and neuron-type-specific transgenic strains, we examined the contribution of neuronal NHR-49 to cell-autonomous and non-autonomous nhr-49 mutant phenotypes. We examined lifespan, brood size, early egg-laying, and reduced locomotion on food. We found that lifespan and brood size could be rescued by neuronal NHR-49, and that NHR-49 in cholinergic and serotonergic neurons is sufficient to restore lifespan. For behavioral phenotypes, NHR-49 in serotonergic neurons was sufficient to control egg-laying, whereas no single tissue or neuron type was able to rescue the enhanced on-food slowing behavior. Our study shows that NHR-49 can function in single neuron types to regulate C. elegans physiology and behavior, and provides a platform to further investigate how lipid metabolism in neurons impact neuronal function and overall health of the organism. [ABSTRACT FROM AUTHOR]

Background: Abnormal lipid metabolism predisposes to cardiovascular disease. However, dyslipidemia is often asymptomatic leading to its underdiagnosis. Therefore, it is of utmost importance to identify biomarkers that reflect an abnormal lipid profile and trigger the specific investigation of lipid metabolism. The platelet–monocyte ratio (PMR) is a severely understudied index whose association with disturbed lipid markers remains unknown. Methods: A cross-sectional study of the association between PMR and comprehensive lipid profile including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), TC/HDL, LDL/HDL, and TG/HDL in 14,269 Saudi subjects was designed. Prevalence, risk measures, association, and the diagnostic performance (i.e., area under the curve (AUC)) were evaluated. Results: Median PMR was significantly elevated in subjects with high TC (p < 0.01), TG, TC/HDL, LDL/HDL, TG/HDL, and LDL and reduced in those with low HDL (all p < 0.0001) compared to normal subjects. The increase in PMR was abolished when only males with high TC were considered. Except for TC and LDL, all other abnormal markers were significantly more prevalent when PMR was lower (higher for HDL) than a certain cutoff specific for each parameter. Moreover, the odds of having PMR readings above or below the selected cutoffs are significantly higher with all lipid abnormalities. PMR was also weakly but significantly and differentially correlated with all forms of dyslipidemia (p < 0.0001). Notably, the highest diagnostic accuracy of PMR was observed for reduced HDL (AUC = 0.608, p < 0.0001) and elevated TG/HDL (AUC = 0.596, p < 0.0001). Conclusions: PMR is a novel, inexpensive, and readily available index that is associated with all forms of dyslipidemia, suggesting its potential use in related disorders. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons. To study its underlying mechanisms, a variety of models are currently used at the cellular level and in animals with mutations in multiple ALS associated genes, including SOD1, C9ORF72, TDP-43, and FUS. Key mechanisms involved in the disease include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammatory, and immune reactions. In addition, significant metabolism alterations of various lipids classes, including phospholipids, fatty acids, sphingolipids, and others have been increasingly recognized. Recently, the mechanisms of programmed cell death (apoptosis), which may be responsible for the degeneration of motor neurons observed in the disease, have been intensively studied. In this context, sphingolipids, which are the most important sources of secondary messengers transmitting signals for cell proliferation, differentiation, and apoptosis, are gaining increasing attention in the context of ALS pathogenesis given their role in the development of neuroinflammatory and immune responses. This review describes changes in lipids content and activity of enzymes involved in their metabolism in ALS, both summarizing current evidence from animal models and clinical studies and discussing the potential of new drugs among modulators of lipid metabolism enzymes. [ABSTRACT FROM AUTHOR]

With the ability to survive under drought and chronic hunger, camels display a unique regulation characteristic of lipid metabolism. Fibroblast growth factor (FGF) 21 is a peptide hormone that regulates metabolic pathways, especially lipid metabolism, which was considered as a promising therapeutic target for metabolic diseases. To understand the FGF21 expression pattern and its potential relationship with lipid metabolism in camels, this study investigated the distribution and expression of FGF21, receptor FGFR1, and two lipid metabolism markers, leptin and hormone-sensitive lipase (HSL), using an immunohistochemistry (IHC) assay. The results showed that FGF21 was widely expressed in camel central nerve tissue and peripheral organs but absent in lung and gametogenic tissue, including the testis, epididymis, and ovary. In striated muscle, FGF21 is only present at the fiber junction. FGFR1 is expressed in almost all tissues and cells, indicating that all tissues are responsive to FGF21 and other FGF-mediated signals. Leptin and HSL are mainly located in metabolic and energy-consuming organs. In the CNS, leptin and HSL showed a similar expression pattern with FGFR1. In addition, leptin expression is extremely high in the bronchial epithelium, which may be due to its role in the immune responses of respiratory mucosa, in addition to fat stores and energy balance. This study found that FGF21 showed active expression in the nervous system of camels, which may be related to the adaptability of camels to arid environments and the specific regulation of lipid metabolism. This study showed a special FGF21-mediated fat conversion pattern in camels and provides a reference for developing a potential therapeutic method for fat metabolism disease. [ABSTRACT FROM AUTHOR]