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Individual SCFA can differentially modulate the adipocyte secretory profile and adipose tissue metabolic function; however, their dose-dependent effects on adipocyte function in combined inflammatory and hypoxic environmental conditions that reflect the obesity-associated adipose tissue phenotype remain unknown. Methods: Mature 3T3-L1 adipocytes were cultured for 24 h with lipopolysaccharide (LPS; 10 ng\/mL) plus 100 \u00b5M of cobalt chloride (CoCl2) to chemically induce hypoxia \u00b1 individual SCFAs, namely acetate (Ace), propionate (Pro), and butyrate (But), in a dose-dependent manner (0.25 mM, 0.5 mM, and 1 mM). Results: Ace, Pro and But reduced secretion of IL-6, MCP-1\/CCL7 and Rantes\/CCL5 in a dose-dependent manner, whereas Pro and But reduced MCP3\/CCL7 secretion and only But reduced resistin and increased adiponectin secretion compared to control (p &lt; 0.05). Intracellular protein expression of the ratio of phosphorylated\u2013to\u2013total NF\u03baB p65 was reduced by 1 mM But, whereas the ratio of phosphorylated\u2013to\u2013total STAT3 expression was reduced by 1 mM Ace, Pro and But and 0.5 mM Pro and But compared to control (p &lt; 0.05). There was no difference in insulin-stimulated or non-insulin-stimulated glucose uptake between control and any individual SCFAs (p &gt; 0.05). Conclusions: Adipocyte adipokine secretory function in combined inflammation and hypoxic environmental conditions is dose-dependently attenuated by individual SCFA, which exhibit both individual and overlapping effects.<\/jats:p>","DOI":"10.3390\/nu18060942","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T10:21:41Z","timestamp":1773742901000},"page":"942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Severity of Hypoxia-Induced Effects on 3T3-L1 Adipocyte Secretory Function Is Attenuated Dose-Dependently by Individual Short-Chain Fatty Acids"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1281-9633","authenticated-orcid":false,"given":"Jessie L.","family":"Burns","sequence":"first","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Van","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ala","family":"Alzubi","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9733-2516","authenticated-orcid":false,"given":"Clara E.","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Monk","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1161\/CIRCRESAHA.120.316101","article-title":"Obesity Phenotypes, Diabetes, and Cardiovascular Diseases","volume":"126","author":"Tchernof","year":"2020","journal-title":"Circ. 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