IGF-1 Mediates Exercise-Induced Phospholipid Alteration in the Murine Skin Tissues

Abstract

Sciences AbstractWe previously demonstrated that exercise with an iso-caloric diet significantly reduced body weight and skin carcinogenesis in correspondence with lower plasma IGF-1 levels and IGF-1-dependent phospholipid signaling. This study was thus designed to test the hypothesis that IGF-1 reduction plays a causal role in exercise-induced phospholipid changes. SENCAR mice were randomly assigned to one of the following three groups for 12 weeks: ad libitum-fed sedentary control, exercise but pair-fed the amount of the control (PE), and PE with IGF-1 injection (PE+IGF-1). Treadmill exercise was conducted at 13.4 m/min for 90 min/d, 5 d/week. In the last two weeks IGF 1 was i.p. injected (10 μg/g B.W.) twice per week. Both body weight and plasma IGF-1 levels were significantly reduced in PE mice when compared with the control. IGF-1 injection did not affect body weight, or the plasma levels of IGF-1 at the end of the experiment due to a rapid degradation with a half-life of 3.4 hrs. Of the 338 phospholipid species detected in the skin tissues by electron spray ionization tandem mass spectrometry, 21 were significantly changed in PE mice compared to control. Fourteen of the altered 21 species in PE mice were reversed by IGF-1 injection, including the most abundant phosphatidylinositol (PI) 38:4, a substrate for lipid PI3K signaling. Western Blot Analysis further showed the reduced PI3K, but not IGF-1R, in PE mice was also reversed by IGF-1 restoration. Overall, these data provided evidence that exercise-induced reduction of IGF-1 is required in mediating the alteration of phospholipid profile and PI-related PI3K signaling.

Reduced signaling of PI3K-Akt and RAS-MAPK pathways is the key target for weight-loss-induced cancer prevention by dietary calorie restriction and/or physical activity

“…36,37 Our lab has shown that IGF-1 restoration within PE mice reversed the reduction of PI phospholipids and PI-associated PI3K. 23 Hence, it appears that IGF-1 is a key growth factor that promotes cancer development in overweight conditions, in part through promoting PI phosphorylation by PI3K and downstream Akt activity which contribute to anti-apoptosis. 38,39 Hence, increased IGF-1-Akt anti-apoptosis, or inhibition of apoptosis, may lead to cancer promotion through turning off protective nuclear apoptosis genes.…”

“…22, 23 In short, each frozen dorsal skin tissue was ground with liquid nitrogen. One gram of tissue was mixed with 2 ml solvent [chloroform/methanol (1:2) + 0.01% butylated hydroxytoluene], 1 ml of chloroform, and 1 ml of water.…”

“…One ml of chloroform was added and the mixture was centrifuged for 15 min at 1,000 rpm followed by collection of the lower layer. The two lower layer extracts were combined for phospholipid analysis using an automated ESI/MS-MS. 22, 23 Phospholipid analysis was able to determine phospholipid classes/subclasses such as Phosphatidic acid, PI, PC, lysoPC, alk(en)yl/acyl phosphocholine (ePC), PE, lysoPE, alk(en)yl/acyl phosphoethanolamine (ePE), phosphatidylserine (PS), alk(en)yl/acyl phosphoserine, sphingomyelin (SM), and ceramide PE. Phospholipid identification was based upon total mass/charge and fragment mass/charge consistent with the head group.…”

Penalized Variable Selection for Lipid–Environment Interactions in a Longitudinal Lipidomics Study

“…Traditionally, the analyses mostly focus on the total amount of a particular type of lipid, such as total triglyceride, total cholesterol, and omega-3 fatty acid. With the recent advances in instrumental technology, it is feasible to analyze quantitatively a broad range of lipid species in a single platform [13,15,[30][31][32]. The vast arrays of data generated in lipid profiling studies bring challenges to the statistical analysis of lipidomics data [33][34][35].…”

Weight control and cancer preventive mechanisms: Role of insulin growth factor-1-mediated signaling pathways

“…93 In addition, a lipidomics study using electrospray ionization-tandem mass spectrometry demonstrated that 57 phospholipids were significantly changed among a total of 338 species detected, and 25 species were closely related to exercise by a stepwise discriminant analysis. 93–94 These combined results indicate that DCR and/or exercise may target IGF-1-dependent signaling directly for a potential cancer prevention.…”