Role of Inflammatory Signaling in the Differential Effects of Saturated and Poly-unsaturated Fatty Acids on Peripheral Circadian Clocks.
Inflammatory signaling may play a role in high-fat diet (HFD)-related circadian clock disturbances that contribute to systemic metabolic dysregulation. Therefore, palmitate, the prevalent proinflammatory saturated fatty acid (SFA) in HFD and the anti-inflammatory, poly-unsaturated fatty acid (PUFA), docosahexaenoic acid (DHA), were analyzed for effects on circadian timekeeping and inflammatory responses in peripheral clocks. Prolonged palmitate, but not DHA, exposure increased the period of fibroblast Bmal1-dLuc rhythms. Acute palmitate treatment produced phase shifts of the Bmal1-dLuc rhythm that were larger in amplitude as compared to DHA. These phase-shifting effects were time-dependent and contemporaneous with rhythmic changes in palmitate-induced inflammatory responses. Fibroblast and differentiated adipocyte clocks exhibited cell-specific differences in the time-dependent nature of palmitate-induced shifts and inflammation. DHA and other inhibitors of inflammatory signaling (AICAR, cardamonin) repressed palmitate-induced proinflammatory responses and phase shifts of the fibroblast clock, suggesting that SFA-mediated inflammatory signaling may feed back to modulate circadian timekeeping in peripheral clocks.
Department of Biology, Texas A&M University, College Station, TX 77843-3258, USA; Center for Biological Clocks Research, Texas A&M University, College Station, TX 77843-3258, USA.
Sam-Moon
SM
Kim
Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807-3260, USA.
Nichole
N
Neuendorff
Program in Integrative Nutrition & Complex Diseases, Center for Translational Environmental Health Research, Texas A&M University, College Station, TX 77843-2253, USA; Department of Nutrition & Food Science, Texas A&M University, College Station, TX 77843-2253, USA; Department of Microbial Pathogenesis and Immunology, Texas A&M University System Health Science Center, College Station, TX 77807-3260, USA. Electronic address: r-chapkin@tamu.edu.
Robert S
RS
Chapkin
Department of Biology, Texas A&M University, College Station, TX 77843-3258, USA; Center for Biological Clocks Research, Texas A&M University, College Station, TX 77843-3258, USA; Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807-3260, USA. Electronic address: dearnest@medicine.tamhsc.edu.
David J
DJ
Earnest
D017667:Adipocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D057906:Circadian Clocks / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D004281:Docosahexaenoic Acids; D019308:Palmitic Acid
AMP-activated protein kinase (AMPK); AMPK; Adipocytes; Aminoimidazole-4-Carboxamide Riboside (AICAR); Bmal1; Cardamonin; Circadian clocks; Cytokines; Fatty acids; Fibroblasts; Inflammation; NF-κB