{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:32:01Z","timestamp":1790519521716,"version":"4.1.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      This study aims to explore the potential therapeutic effect of\n                      <jats:italic>Dendrobium officinale<\/jats:italic>\n                      polysaccharide (DOP) on non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD), and to elucidate the underlying mechanism involving the SIRT6\/PGC-1\u03b1 signaling axis and the regulation of the gut microbiota.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We extracted and characterized DOP. We established a rat model of NAFLD induced by HFD and evaluated the efficacy of DOP by integrating multi-omics techniques (transcriptomics, metabolomics) and 16S rRNA sequencing. To verify the specific role of SIRT6, we introduced the SIRT6 inhibitor OSS_128167 in the primary hepatocyte model induced by oleic acid\/palmitic acid (OA\/PA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DOP significantly alleviated liver steatosis, oxidative stress, and lipid metabolism disorders induced by HFD. Multi-omics analysis indicated that DOP regulated liver glycerophospholipid metabolism and restored intestinal microbiota homeostasis, significantly increasing the abundance of beneficial bacteria such as\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      . Mechanistically, DOP activated the liver SIRT6\/PGC-1\u03b1 signaling axis, thereby enhancing antioxidant defense and inhibiting lipogenesis. Crucially,\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments confirmed that the SIRT6 inhibitor OSS_128167 eliminated the protective effect of DOP on lipid accumulation, confirming that the effect of DOP depends on SIRT6.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DOP improves NAFLD through dual mechanisms of regulating the gut-liver axis homeostasis and directly activating the liver SIRT6\/PGC-1\u03b1 signaling pathway. The results of this study provide a theoretical basis for developing DOP as a drug for the treatment of NAFLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1763341","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T17:07:40Z","timestamp":1780420060000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dendrobium officinale polysaccharide ameliorates high-fat diet-induced hepatic lipid metabolic disorder via the SIRT6\/PGC-1\u03b1 signaling axis"],"prefix":"10.3389","volume":"13","author":[{"given":"Binhong","family":"Hu","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing University of Chinese Medicine","place":["Chongqing, China"]},{"name":"College of Chemistry and Life Sciences, Chengdu Normal University","place":["Chengdu, Sichuan, China"]},{"name":"Department of Medical Biochemistry and Microbiology, Uppsala 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