Dietary sodium restriction alters muscle lipidomics that relates to insulin resistance in mice

• Published in: The Journal of biological chemistry Vol. 296; p. 100344
• Main Authors: Pinto, Paula Ramos, Yoshinaga, Marcos Y., Del Bianco, Vanessa, Bochi, Ana Paula, Ferreira, Guilherme S., Pinto, Isabella F.D., Rodrigues, Letícia G., Nakandakare, Edna R., Okamoto, Maristela M., Machado, Ubiratan F., Miyamoto, Sayuri, Catanozi, Sergio, Passarelli, Marisa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2021; American Society for Biochemistry and Molecular Biology
• Subjects: insulin resistance; lipid metabolism; lipidomics; low-sodium diet; skeletal muscle; FFA; IRS-1; NS; JNK; lipid metabolism; LS; RAAS; BM; BP; kITT; SM; skeletal muscle; insulin resistance; FPLC; AC; pPE; CL; IR; IGF-1; TC; CVD; low-sodium diet; LDLR KO; PC; TG; PE; ROS; AMPK; PI; lipidomics; CPT-1
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/j.jbc.2021.100344

A low-sodium (LS) diet has been shown to reduce blood pressure (BP) and the incidence of cardiovascular diseases. However, severe dietary sodium restriction promotes insulin resistance (IR) and dyslipidemia in animal models and humans. Thus, further clarification of the long-term consequences of LS is needed. Here, we investigated the effects of chronic LS on gastrocnemius gene and protein expression and lipidomics and its association with IR and plasma lipids in LDL receptor knockout mice. Three-month-old male mice were fed a normal sodium diet (NS; 0.5% Na; n = 12–19) or LS (0.06% Na; n = 14–20) over 90 days. Body mass (BM), BP, plasma total cholesterol, triacylglycerol (TG), glucose, hematocrit, and IR were evaluated. LS increased BM (9%), plasma TG (51%), blood glucose (19%), and IR (46%) when compared with the NS. RT-qPCR analysis revealed that genes involved in lipid uptake and oxidation were increased by the LS: Fabp3 (106%), Prkaa1 (46%), and Cpt1 (74%). Genes and proteins (assessed by Western blotting) involved in insulin signaling were not changed by the LS. Similarly, lipid species classically involved in muscle IR, such as diacylglycerols and ceramides detected by ultra-high-performance liquid chromatography coupled to mass spectrometry, were also unchanged by LS. Species of phosphatidylcholines (68%), phosphatidylinositol (90%), and free fatty acids (59%) increased while cardiolipins (41%) and acylcarnitines (9%) decreased in gastrocnemius in response to LS and were associated with glucose disposal rate. Together these results suggest that chronic LS alters glycerophospholipid and fatty acids species in gastrocnemius that may contribute to glucose and lipid homeostasis derangements in mice.