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NO is an important cellular signalling molecule that regulates lipid and glucose metabolism. The biological availability of NO is affected by the NOS inhibitor; N\n                    <jats:sup>G<\/jats:sup>\n                    -nitro-L-Arg methyl ester (L-NAME) and the external NO donor; S-nitroso-N-acetyl-D, L-penicillamine (SNAP). Mouse adipocyte 3T3 L1 cells were cultured with 0, 400 and 800\u00a0\u00b5M L-Arg or control complete DMEM media. The impact of L-NAME (4\u00a0mM), and SNAP (100\u00a0\u00b5M) was also analysed. The cell fitness was similar and the mRNA levels of AMPK was increased and ACC-1 was decreased, whilst the activation of AMPK and ACC-1 was decreased upon the addition of exogenous L-Arg. Transcript and protein levels of AMPK and ACC-1 were regulated by addition of L-NAME and SNAP, however the impact of these targets was related to the concentration of L-Arg added to the cells and the culture time point of analysis. NO in the form of NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    in cell culture supernatant was elevated in 400 and 800\u00a0\u00b5M L-Arg cultures. L-NAME significantly inhibited NO production from adipose cells in a time-dependent manner and subsequently impacted AMPK and ACC expression. Associated with these changes were changed in the concentration of L-Arg, L-Cit and L-Orn in the culture media. Collectively, these results show that excess L-Arg is sensed by the cell which then regulates AMPK and ACC-1 expression in response. The findings could have implications in modulation of signalling pathways for treating obesity and obesity induced diabetic mellitus.\n                  <\/jats:p>","DOI":"10.1007\/s00726-025-03467-0","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T16:03:26Z","timestamp":1754409806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The effect of L-Arg supplementation on L-Arg\/NO metabolic and AMPK\/ACC-1 signalling pathways in adipose cells (3T3 L1)"],"prefix":"10.1007","volume":"57","author":[{"given":"Saranya","family":"Prashath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"issue":"3","key":"3467_CR1","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1042\/bj3570593","volume":"357","author":"WK Alderton","year":"2001","unstructured":"Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. 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