Intracellular Lipid Accumulation in Liver and Muscle and the Insulin Resistance Syndrome

Department of Nutrition Sciences, University of Alabama at Birmingham, 1675 University Boulevard,Birmingham, AL 35294-3360, USA.
Endocrinology and metabolism clinics of North America (Impact Factor: 3.4). 01/2009; 37(4):841-56. DOI: 10.1016/j.ecl.2008.09.002
Source: PubMed


This article emphasizes intrahepatocellular and intramyocellular lipid accumulation as components of the insulin resistance syndrome. It examines the mechanisms responsible for the interrelationships among ectopic fat deposition, insulin resistance, and associated metabolic traits. These relationships are complex and vary according to diet, exercise, weight loss, and racial identity. Overall, there is a high degree of association of both intrahepatocellular and intramyocellular lipids with insulin resistance and associated cardiometabolic risk factors. It concludes that further research is necessary to determine the orchestrated roles of adipose and nonadipose tissue compartments in the regulation of insulin sensitivity, and mechanisms explaining racial differences in the insulin resistance syndrome-trait cluster.

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    • "Greater intramuscular fat content in BSCP may expose these individuals to a greater risk of developing cardio-metabolic disease [20]. There is a strong relationship between intramuscular fat content, insulin resistance and type-II diabetes [15,35,36]. Within skeletal muscle, fat is stored in two separate compartments: Intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL). "
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    ABSTRACT: Background It is known that individuals with bilateral spastic cerebral palsy (BSCP) have small and weak muscles. However, no studies to date have investigated intramuscular fat infiltration in this group. The objective of this study is to determine whether adults with BSCP have greater adiposity in and around their skeletal muscles than their typically developing (TD) peers as this may have significant functional and cardio-metabolic implications for this patient group. Methods 10 young adults with BSCP (7 male, mean age 22.5 years, Gross Motor Function Classification System (GMFCS) levels I-III), and 10 TD young adults (6 male, mean age 22.8 years) took part in this study. 11 cm sections of the left leg of all subjects were imaged using multi-echo gradient echo chemical shift imaging (mDixon). Percentage intermuscular fat (IMAT), intramuscular fat (IntraMF) and a subcutaneous fat to muscle volume ratio (SF/M) were calculated. Results IntraMF was higher with BSCP for all muscles (p = 0.001-0.013) and was significantly different between GMFCS levels (p < 0.001), with GMFCS level III having the highest IntraMF content. IMAT was also higher with BSCP p < 0.001). No significant difference was observed in SF/M between groups. Conclusion Young adults with BSCP have increased intermuscular and intramuscular fat compared to their TD peers. The relationship between these findings and potential cardio-metabolic and functional sequelae are yet to be investigated.
    BMC Musculoskeletal Disorders 07/2014; 15(1):236. DOI:10.1186/1471-2474-15-236 · 1.72 Impact Factor
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    • "The latter is also known as ectopic lipid accumulation and may be linked to insulin resistance and í µí»½ cell dysfunction [4] [5]. In the skeletal muscle and liver, fat deposition has been associated with the development of insulin resistance [6] [7]. In the pancreatic islets, FFA and triglycerides accumulation induce í µí»½ cell functional impairment and lipoapoptosis [8]. "
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    ABSTRACT: Jiao Tai Wan (JTW), a Chinese herbal formula containing Rhizoma Coptidis and Cortex Cinnamomi, has been used for diabetic treatment for many years. The aim of this study was to determine the main components in JTW and to investigate the effects of JTW on hepatic lipid accumulation in diabetic rats and humans. JTW extract was prepared and the main components were assayed by HPLC. An animal model of diabetes mellitus was established and JTW was administered intragastrically. In the clinical study, diabetic patients with poor glycemic control were treated with JTW. Blood glucose and lipid parameters, liver histology, hepatic triglyceride content and lipogenic gene expression were examined. Our data demonstrated that JTW significantly improved hyperglycemia, hyperlipidemia and hepatic lipid accumulation in diabetic rats. This was accompanied by the down-regulation of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) protein expressions, and the up-regulation of AMP-activated protein kinase (AMPK) and phosphorylated-ACC (pACC) protein expressions in the liver tissues. Diabetic patients also exhibited decreases in their hepatic triglyceride content. The results suggest that JTW attenuates hepatic lipid accumulation in diabetic rats and humans. These beneficial effects are possibly associated with the inhibition of lipogenic gene expression in the liver.
    Evidence-based Complementary and Alternative Medicine 11/2013; 2013(4):567045. DOI:10.1155/2013/567045 · 1.88 Impact Factor
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    • "IHCL have been demonstrated to be linked to markers of insulin resistance [14]–[17]. In addition, several data suggest that fat mass, in particular visceral fat mass, is positively correlated with IHCL [14]–[17] suggesting that the availability of fat (fat mass and circulatory free fatty acids; FFA) may be involved in mediating the impaired insulin action at the hepatic level [18]. "
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    ABSTRACT: Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects over a broad range of exercise capacity. IMCL and IHCL have been related to impaired insulin action at the skeletal muscle and hepatic level, respectively. The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory factors include exercise capacity, insulin sensitivity and fat availability subcutaneous and visceral fat mass). To concomitantly investigate the effect of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic Resonance spectroscopy. Normal weight, healthy subjects were included. Visit 1 consisted of a determination of VO2max on a treadmill. Visit 2 comprised the assessment of hepatic and peripheral insulin sensitivity by a two-step hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours aerobic exercise (50% of VO2max) using (1)H-MR-spectroscopy. Eighteen volunteers (12M, 6F) were enrolled in the study (age, 37.6±3.2 years, mean±SEM; VO2max, 53.4±2.9 mL/kg/min). Two hours aerobic exercise resulted in a significant decrease in IMCL (-22.6±3.3, % from baseline) and increase in IHCL (+34.9±7.6, % from baseline). There was no significant correlation between the exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and visceral fat mass and hepatic or peripheral insulin sensitivity. IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by physical exercise, albeit in different directions. NCT00491582.
    PLoS ONE 08/2013; 8(8):e70865. DOI:10.1371/journal.pone.0070865 · 3.23 Impact Factor
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