Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats.
Manuel A CornejoJaapna DhillonAkira NishiyamaDaisuke NakanoRudy M OrtizPublished in: PloS one (2021)
Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, Pearson correlation vs previously reported variables (adipose and body masses, and insulin resistance index, IRI), and metabolomics maps (MetaMapp) generated for the most significant group comparisons. All treatments elicited a significant group differentiation in at least one principal component. CR improved TCA cycle in OLETF, and increased lipolysis and proteolysis. These changes were reversed after PR except for gluconeogenesis. Plasma lipid concentrations were inversely correlated to IRI in LETO, but not OLETF. These shifts in substrate metabolism suggest that the CR-induced decreases in adipose may not be sufficient to more permanently alter substrate metabolism to improve IR status during metabolic syndrome.
Keyphrases
- study protocol
- insulin resistance
- mass spectrometry
- gas chromatography
- adipose tissue
- metabolic syndrome
- randomized controlled trial
- liquid chromatography
- type diabetes
- data analysis
- high fat diet
- skeletal muscle
- polycystic ovary syndrome
- high fat diet induced
- high performance liquid chromatography
- high resolution mass spectrometry
- high resolution
- capillary electrophoresis
- ms ms
- tandem mass spectrometry
- magnetic resonance imaging
- magnetic resonance
- electronic health record
- machine learning
- multiple sclerosis
- acute respiratory distress syndrome
- structural basis
- ultrasound guided
- fine needle aspiration
- liver failure
- intensive care unit
- body mass index
- contrast enhanced ultrasound
- oxidative stress