ABSTRACT
IL-6 is a biologically active substance which appears to be involved in regulating skeletal muscle lipid oxidation. Ablation of IL-6 (IL-6(-/-)) may therefore be expected to increase intracellular lipid accumulation, possibly via a concurrent increase in fatty acid transporters such as FAT/CD36 and FABPpm. This however may only occur in oxidative muscles which utilize fatty acids at a greater rate than glycolytic muscles. In the present study we examined the fatty acid transporter protein expression as well as the lipid content and profiles of free fatty acids (FFA), diacylglycerols (DGs) and triacylglycerols (TGs) in skeletal muscles of IL-6 deficient mice at 4 and 12 months of age. FAT/CD36 and FABPpm protein content was increased in red muscles in IL-6(-/-) mice compared to WT mice at 4 (RG) and 12 months (soleus and RG). Along with this, FFA, DG and TG concentrations were also increased in these red IL-6(-/-) muscles. In addition, the IL-6(-/-) genotype increased the saturated FA acid composition of the intramuscular TG fraction. In contrast, in white gastrocnemius muscle the IL-6(-/-) genotype has no effect on the expression of fatty acid transporters as well as the lipid content and composition at either 4 mo or 12 months of age. IL-6 ablation increases fatty acid transporter expression and intramuscular lipid accumulation, particularly the saturated fatty acids. These effects however were confined to oxidative muscles, as glycolytic muscles were not affected.
Subject(s)
CD36 Antigens/metabolism , Fatty Acid Transport Proteins/metabolism , Fatty Acid-Binding Proteins/metabolism , Interleukin-6/genetics , Muscle, Skeletal/metabolism , Age Factors , Animals , Diglycerides/metabolism , Fatty Acids, Nonesterified/metabolism , Female , Mice , Mice, Inbred C57BL , Mice, Knockout , Triglycerides/metabolismABSTRACT
IL-6 is a biologically active substance and is thought to contribute to the development of obesity. Recent findings suggest that susceptibility to intracellular lipid accumulation is to a large extent determined by changes in the expression of fatty acid transporters such as FAT/CD36, FABPpm and FATP-1. The aim of the present study was to determine the effect of IL-6 deficiency on the expression of fatty acid transporters, as well as, assess the concomitant changes in intracellular lipids. We found that Il-6 deficiency upregulated the myocardial expression of FAT/CD36 (+40%) and did not significantly affect the content of FABPpm and FATP-1 (+15% and +5% respectively). Although no change in the intramyocardial total lipid content was noted, there was a significant increase in the intracellular content of both free fatty acid (FFA), diacylglicerol (DG) and ceramide fractions (+45%, +37% and +48%, respectively) in hearts from IL-6 -/- mice. A trend for IL-6 deficiency to increase in saturated FA species in these fractions was also observed (+8%, +12% and +10%, respectively). In contrast, IL-6 deficiency has no effect on the content of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) species in each intramyocardial lipid fractions examined. These findings suggest that IL-6 deficiency results in 1) upregulation of myocardial content of FAT/CD36, 2) the increase in the content of biologically active lipid pools (FFA, DG and ceramide). This lipid accumulation with concomitant trend for increase in the saturation status of these lipid fractions may, at least in part, provide a factor related to the development of intramyocardial lipotoxicity, observed in obese individuals.
Subject(s)
Fatty Acid Transport Proteins/metabolism , Interleukin-6/deficiency , Lipid Metabolism , Myocardium/metabolism , Animals , CD36 Antigens/metabolism , Ceramides/metabolism , Diglycerides/metabolism , Fatty Acids, Nonesterified/metabolism , Female , Interleukin-6/genetics , Mice , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
A case of a 36-year patient with persistent diabetes mellitus of type I and gangrene of the foot is presented. Calcitonin has been used to treat osteitis and inflammation of the adjacent soft tissues. Despite performed surgery and conservative treatment, destruction of the bones has been progressing, and could lead to the high amputation of the extremity. Calcitonin produced an increase in bone, massive calcification around bone stumps, and anastomosis within one year. An acceleration of the wound healing has also been noted. Taking calcitonin mechanism of action and the clinical course of this case into consideration, it seems justified to use calcitonin in the treatment of gangrene of the foot in diabetes.
