Muscle lipid metabolism

Fatty acids are clearly larger in size and show markedly slower diffusion velocity than the small water (or creatine) molecules which have been examined so far by diffusion weighted NMR spectroscopy. However, assessment of diffusion properties of lipids could be a key step for further experimental studies of skeletal muscle lipid metabolism. Diffusion properties of FFA and triglycerides are likely different due to differences in molecular weight. In addition, effects of temperature, chemical surroundings, and the mobility of small lipid droplets in the cytosol may also lead to measurable differences in the diffusion characteristics. 

Bank WJ, DiMauro S, Bonilla E, Capuzzi DM, Rowland LP. A disorder of muscle lipid metabolism and myoglobinuria. Absence of carnitine palmityl transferase. N Engl J Med. 1975 292(9) 443-9. PubMed PMID 123038, Epub 1975/02/27. eng. 

One class of glycogen or lipid metabolic disorders in muscle is manifest as acute, recurrent, reversible dysfunction 696... 

An increasing number of studies on lipid metabolism in human skeletal muscle using localized MR proton spectroscopy have been performed since the first description of the phenomenon that proton NMR spectroscopy allows the differentiation of two distinct lipid compartments and the experimental confirmation that one of these compartments is attributed to the IMCL pool. The non-invasiveness and the high sensitivity even to low lipid concentrations under physiological conditions denote the uniqueness of this modality and allow examinations of large numbers of healthy volunteers and follow-up metabolic intervention studies. 

A brief overview about the fundamental principles of the pathogenesis of skeletal muscle insulin resistance and its contribution to the development of type 2 diabetes mellitus is given in the following. Priority is given to the role of lipid metabolism, which is the main field of the reported spectroscopic studies. Furthermore, the technique of euglycemic hyperinsulinemic glucose clamp is described allowing determination of the individual insulin sensitivity of musculature. The role of IMCL in insulin resistance of the skeletal muscle is discussed. 

Lipid metabolism and skeletal muscle insulin resistance... 

Lipid metabolism in the liver is closely linked to the carbohydrate and amino acid metabolism. When there is a good supply of nutrients in the resorptive (wellfed) state (see p. 308), the liver converts glucose via acetyl CoA into fatty acids. The liver can also take up fatty acids from chylomicrons, which are supplied by the intestine, or from fatty acid-albumin complexes (see p. 162). Fatty acids from both sources are converted into fats and phospholipids. Together with apoproteins, they are packed into very-low-density lipoproteins (VLDLs see p.278) and then released into the blood by exocytosis. The VLDLs supply extrahepatic tissue, particularly adipose tissue and muscle. 

The answer is A. Recent research has revealed that excess visceral fat deposits secrete several factors that have direct effects on the brain as well as directly on muscle to produce peripheral insulin resistance. Some of these newly identified factors are leptin, re-sistin, and adiponectin, whose mechanisms of action are still under active investigation. Death of pancreatic beta cells is a hallmark feature of type 1 diabetes and may occur only in very advanced stages of type 2 diabetes. Excess adipose in the thighs and buttocks does not contribute as strongly to insulin resistance as does visceral fat, presumably due to a lower level of endocrine activity of such fat depots. Dysfunction of liver lipid metabolism is more a consequence of excess activity of adipose than a cause of insulin resistance. A sedentary lifestyle contributes to build-up of excess fat stores but does not act directly to induce insulin resistance. 

GH administered to hypophysectomized rats in vivo causes a drop in the level of plasma non-esterified fatty acids (NEFA), followed by a prolonged increase in this level [89]. This appears to be due to increased utilization of lipids - increased uptake of NEFA by muscle preceding increased output by adipose tissue. As a consequence GH diverts the energy metabolism of the organism from carbohydrate utilization to lipid utilization, and acts to oppose the effects of insulin. Actions of GH on lipid metabolism are particularly marked in man, where GH levels become elevated on fasting and presumably serve to help stimulate the increased lipid utilization seen in this condition. In contrast, in the rat, GH levels fall on fasting. 

Michael MD, Kulkami RN, Postic C et al. (2000) Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 6 87-97 Neumann-Haefelin C, Beha A, Kuhlmann J et al. (2004) Muscle-type specific intramyocellular and hepatic lipid metabolism during starvation in Wistar rats. Diabetes 53 528-534... 

The authors suggested that this patient had a defect in lipid metabolism, based on the muscle biopsy. Muscle mitochondria are a principle site for beta-oxidation of fatty acids. Microvesicular steatosis can progress to liver failure with severe and prolonged impairment of beta-oxidation. This metabolic defect may have exacerbated the direct toxic effects of cocaine. 

Costlll, D, L., Fink, W. J., Getchell, L. H., Ivy, J. L. and Wltzmann, F. A. (1979) Lipid metabolism In skeletal muscle of endurance trained males and females. J. Appl. Physiol. Resplrat, Environ. Exercise Physiol. 47 787-91. 

ACSL, have a significant impact on fatty acid uptake and trafficking in the major lipid metabolizing organs (intestine, Uver, muscle, and adipose tissue), in the pancreas, and in vascular tissues. 

Propofol infusion syndrome mimics the mitochondrial myopathies, in which there are specific defects in the mitochondrial respiratory chain. The clinical features of mitochondrial myopathy result from a disturbance in lipid metabolism in cardiac and skeletal muscle. These patients generally remain well until stressed by infection or starvation, although subclinical biochemical abnormalities of mitochondrial transport can be demonstrated. It has been suggested that early management of critically iU children may not include adequate calorific intake to balance the increase in metabolic demands, and that in susceptible children the diversion of metabolism to fat substrates may cause the propofol infusion sjmdrome. It is unclear if the dose or duration of propofol infusion alters this effect. As adults have larger carbohydrate stores and require lower doses of propofol for sedation, this may account for the relative rarity of the sjmdrome in adults. The authors suggested that adequate early carbohydrate intake may prevent the propofol infusion syndrome (71). 

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