l-663536 and Obesity
l-663536 has been researched along with Obesity* in 3 studies
Other Studies
3 other study(ies) available for l-663536 and Obesity
Article | Year |
---|---|
Oleic acid stimulates monoamine efflux through PPAR-α: Differential effects in diet-induced obesity.
Obesity continues to be a growing health concern around the world, and elevated levels of free fatty acids as a result of high-fat intake might play a role in neuroendocrine alterations leading to obesity. However, it is unclear how fatty acids affect neuroendocrine functions and energy metabolism. Since hypothalamic monoamines play a crucial role in regulating neuroendocrine functions relating to energy balance, we investigated the direct effects of oleic acid on hypothalamic monoamines and hypothesized that oleic acid would activate peroxisome proliferator-activated receptor alpha (PPAR-α), a nuclear transcription factor involved with fatty acid metabolism, to affect monoamines. We also hypothesized that this response would be subdued in diet-induced obesity (DIO). To test these hypotheses, hypothalami from Sprague Dawley and DIO rats were incubated with 0 (Control), 0.00132 mM, 0.132 mM, 1.32 mM oleic acid, 50 μM MK 886 (a selective PPAR- α antagonist), or oleic acid + MK 886 in Krebs Ringers Henseleit (KRH) solution. HPLC-EC was used to measure monoamine levels in perfusates. Oleic acid produced a significant increase in norepinephrine, dopamine, and serotonin levels in a dose-dependent manner, and incubation with MK886 blocked these effects. The effect of oleic acid on hypothalamic monoamines was attenuated in DIO rats. These findings suggest that PPARα probably plays an essential role in fatty acid sensing in the hypothalamus, by affecting monoamine efflux and DIO rats are resistant to the effects of oleic acid. Topics: Animals; Diet, High-Fat; Dopamine; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Hypothalamus; Indoles; Male; Norepinephrine; Obesity; Oleic Acid; PPAR alpha; Rats; Rats, Sprague-Dawley; Serotonin | 2020 |
Microparticles Carrying Peroxisome Proliferator-Activated Receptor Alpha Restore the Reduced Differentiation and Functionality of Bone Marrow-Derived Cells Induced by High-Fat Diet.
Metabolic pathologies such as diabetes and obesity are associated with decreased level of circulating and bone marrow (BM)-derived endothelial progenitor cells (EPCs). It is known that activation of peroxisome proliferator-activated receptor alpha (PPARα) may stimulate cell differentiation. In addition, microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, are able to reprogram EPCs. Here, we evaluated the role of MPs carrying PPARα on both phenotype and function of progenitor cells from mice fed with a high-fat diet (HFD). HFD reduced circulating EPCs and, after 7 days of culture, BM-derived EPCs and monocytic progenitor cells from HFD-fed mice displayed impaired differentiation. At the same time, we show that MPs bearing PPARα, MPs Topics: Animals; Bone Marrow Cells; Cell Differentiation; Cell-Derived Microparticles; Cells, Cultured; Cellular Reprogramming; Diet, High-Fat; Indoles; Lipoxygenase Inhibitors; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Physiologic; Obesity; PPAR alpha; Stem Cell Niche; Stem Cells | 2018 |
5-Lipoxygenase-activating protein: a potential link between innate and adaptive immunity in atherosclerosis and adipose tissue inflammation.
Transforming growth factor-beta (TGF-beta) is a major antiinflammatory mediator in atherosclerosis. Transgenic ApoE(-/-) mice with a dominant-negative TGFbeta type II receptor (dnTGFbetaRII) on CD4(+) and CD8(+) T cells display aggravated atherosclerosis. The aim of the present study was to elucidate the mechanisms involved in this enhanced inflammatory response. Gene array analyses identified the 5-lipoxygenase-activating protein (FLAP) among the most upregulated genes in both the aorta and adipose tissue of dnTGFbetaRII transgenic ApoE(-/-) mice compared with their ApoE(-/-) littermates, a finding that was confirmed by real-time quantitative RT-PCR. Aortas from the former mice in addition produced increased amounts of the lipoxygenase product leukotriene B(4) after ex vivo stimulation. FLAP protein expression in both the aorta and adipose tissue was detected in macrophages, but not in T cells. Four weeks of treatment with the FLAP inhibitor MK-886 (10 mg/kg in 1% tylose delivered by osmotic pumps) significantly reduced atherosclerotic lesion size and T-cell content. Finally, FLAP mRNA levels were upregulated approximately 8-fold in adipose tissue derived from obese ob/ob mice. In conclusion, the results of the present study suggest a key role for mediators of the 5-lipoxygenase pathway in inflammatory reactions of atherosclerosis and metabolic disease. Topics: 5-Lipoxygenase-Activating Proteins; Adaptation, Physiological; Adipose Tissue; Animals; Aorta; Atherosclerosis; Carrier Proteins; Female; Immunity; Immunity, Innate; Indoles; Leukotriene B4; Lipoxygenase Inhibitors; Macrophages; Male; Membrane Proteins; Mice; Mice, Knockout; Mice, Obese; Obesity; Panniculitis; RNA, Messenger; T-Lymphocytes; Up-Regulation | 2007 |