Myosin 1c: A novel regulator of glucose uptake in brown adipocytes

Objective: The potential of brown adipose tissue (BAT) to influence energy homeostasis in animals and humans is encouraging as this tissue can increase fatty acid and glucose utilization to produce heat through uncoupling protein 1 (UCP1), but the actual mechanism of how the cell regulates glucose uptake is not fully understood. Myosin 1c (Myo1c) is an unconventional motor protein involved in several cellular processes, including insulin-mediated glucose uptake via GLUT4 vesicle fusion in white adipocytes, but its role in glucose uptake in BAT has not previously been investigated. Methods: Using the specific inhibitor pentachloropseudilin (PClP), a neutralizing antibody assay, and siRNA, we examined the role of Myo1c in mechanisms leading to glucose uptake both in vitro in isolated mouse primary adipocytes and in vivo in mice. Results: Our results show that inhibition of Myo1c removes insulin-stimulated glucose uptake in white adipocytes, while inducing glucose uptake in brown adipocytes, independent of GLUT4, by increasing the expression, translation, and translocation of GLUT1 to the plasma membrane. Inhibition of Myo1c leads to the activation of PKA and downstream substrates p38 and ATF-2, which are known to be involved in the expression of β-adrenergic genes. Conclusions: Myo1c is a PKA repressor and regulates glucose uptake into BAT

Emerging Role of Epigenetics in Explaining Relationship of Periodontitis and Cardiovascular Diseases

Cardiovascular diseases such as ischemic heart diseases or stroke are among the leading cause of deaths globally, and evidence suggests that these diseases are modulated by a multifactorial and complex interplay of genetic, environmental, and lifestyle factors. Genetic predisposition and chronic exposure to modifiable risk factors have been explored to be involved in the pathophysiology of CVD. Environmental factors contribute to an individual’s propensity to develop major cardiovascular risk factors through epigenetic modifications of DNA and histones via miRNA regulation of protein translation that are types of epigenetic mechanisms and participate in disease development. Periodontal disease (PD) is one of the most common oral diseases in humans that is characterized by low-grade inflammation and has been shown to increase the risk of CVDs. Risk factors involved in PD and CVD are determined both genetically and behaviorally. Periodontal diseases such as chronic inflammation promote DNA methylation. Epigenetic modifications involved in the initiation and progression of atherosclerosis play an essential role in plaque development and vulnerability. Epigenetics has opened a new world to understand and manage human diseases, including CVDs and periodontal diseases. Genetic medicine has started a new era of epigenetics to overcome human diseases with various new methodology. Epigenetic profiling may aid in better diagnosis and stratification of patients showing potential predisposed states for disease. A better understanding of the exact regulatory mechanisms of epigenetic pathways driving inflammation is slowly emerging and will aid in developing novel tools for the treatment of disease

Evaluation of Turmeric Nanoparticles as Anti-Gout Agent: Modernization of a Traditional Drug

Background and objectives: Turmeric has assisted in the control of inflammation and pain for decades and has been used in combination with other nutraceuticals to treat acute and chronic osteoarthritis pain. Recently, the effect of turmeric, turmeric extract, or curcuminoids on musculoskeletal pain, either by themselves or in conjunction with other substances, has been reported. The aim of this study was to develop and characterize turmeric nanoparticles (T-NPs) for various parameters, both in vitro and in vivo. Materials and Methods: The T-NPs were successfully synthesized and characterized using particle size analysis, solubility improvement, SEM, EDX, X-ray diffraction, and in vivo antigout activity in mice model. Results: The T-NPs were of about 46 nm in size with a positive zeta potential +29.55 ± 3.44 and low polydispersity index (PDI) (0.264). Furthermore, the diseased mice, with induced gout via monosodium urate crystals, were treated with 5, 10, and 20 ppm T-NPs, administered orally, and the anti-gout potential was observed through measurement of joint diameter and changes in biochemical parameters, including lipid profile, renal function test, and liver function tests which significantly reduced the levels of these biochemical parameters. Conclusions: Uric acid levels were significantly reduced after the treatment with T-NPs. indicating that T-NPs show superior potential against gout management. Thus, T-NPs can be developed as an efficient antigout agent with minimum toxicities

Isothermal microcalorimetry measures UCP1-mediated thermogenesis in mature brite adipocytes

International audienceAbstract The activation of thermogenesis in adipose tissue has emerged as an important target for the development of novel anti-obesity therapies. Using multi-well isothermal microcalorimetry, we have demonstrated that mature murine brown and brite adipocytes produce quantifiable heat upon β 3 -AR stimulation, independently of any anaerobic mechanisms. Additionally, in brite adipocytes lacking UCP1 protein, β 3 -AR stimulation still induces heat production, albeit to a much lower extent than in their wildtype counterparts, suggesting that UCP1 is an essential component of adrenergic induced thermogenesis in murine brite adipocytes exvivo. Similarly, we could observe an increase in heat production in human-derived adipocytes (hMADS) upon β-AR stimulation. Collectively, these results establish the use of isothermal microcalorimetry as a sensitive and accurate technique for measuring thermogenic responses in intact mature brite adipocytes from murine and human origin