Nonalcoholic fatty liver disease is associated with hepatic and skeletal muscle insulin resistance in overweight adolescents

Deivanayagam, Sheela; Mohammed, B. Selma; Vitola, Bernadette; Naguib, Gihan H; Keshen, Tamir H.; Kirk, Erik P.; Klein, Samuel

doi:10.1093/ajcn/88.2.257

Cited by 104 publications

(99 citation statements)

References 43 publications

(41 reference statements)

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“…30 Glucose uptake by muscle is impaired in NAFLD. 31 The inability to exercise and particularly exercise strenuously, removes an effective treatment for people with both NAFLD and DM. More data will be needed to determine the extent of the impact of dual diagnoses on exercise tolerance.…”

Section: Discussionmentioning

confidence: 99%

Non‐alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population‐based study

Gerber

Otgonsuren

Mishra

et al. 2012

Aliment Pharmacol Ther

216

117

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Section: Discussionmentioning

confidence: 99%

Non‐alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population‐based study

Gerber

Otgonsuren

Mishra

et al. 2012

Aliment Pharmacol Ther

216

117

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“…IHTG content was used to identify subjects who were either MNO (IHTG <5.6%, n = 12, age = 43 ± 10 years, 2 males, 5 African-Americans, 1 Native-American, and 6 subjects of mixed European descent) or MAO (IHTG >10%, n = 8, age = 52 ± 7 years, 4 males, 2 African-Americans, and 6 subjects of mixed European descent), because increased IHTG content is a robust marker of inappropriate fat distribution and metabolic dysfunction (3,7,37). All subjects completed a comprehensive medical evaluation.…”

Section: Subjectsmentioning

confidence: 99%

Metabolically normal obese people are protected from adverse effects following weight gain

Fabbrini¹,

Yoshino²,

Yoshino³

et al. 2015

J. Clin. Invest.

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145

150

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BACKGROUND.Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as "metabolically normal obese" (MNO), but not those defined as "metabolically abnormal obese" (MAO), are protected from the adverse metabolic effects of weight gain. METHODS.Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m 2 who were matched for BMI and fat mass. RESULTS.Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects.CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain-induced metabolic dysfunction.TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170.

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“…The pathogenesis of these conditions occurs in insulin-acting peripheral tissues, including skeletal muscle, liver, and adipose tissue. [1][2][3] In particular, insulin resistance-related adipose tissue dysfunction leads to the release of a high level of free-fatty acids and perturbs the levels of various adipokines, such as leptin, adiponectin, and retinol binding protein 4 (RBP4), which directly or indirectly affect insulin sensitivity by modulating insulin signaling and molecules involved in glucose and lipid metabolism in many tissues. [4][5][6] RBP4 is a compact, globular, 21-kDa protein and was known only as a retinol carrier synthesized and secreted by the liver, until recently.…”

mentioning

confidence: 99%

Fenretinide Ameliorates Insulin Resistance and Fatty Liver in Obese Mice

Koh

Jun

Choi

et al. 2012

Biological & Pharmaceutical Bulletin

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Fenretinide (FEN), a ligand of retinol binding protein 4 (RBP4), has been suggested as a measure to reduce insulin resistance and its associated disorders such as obesity, and fatty liver by reducing serum RBP4. We investigated whether there is another possible mechanism by which fenretinide reduces insulin resistance and fatty liver in genetically obese (ob/ob) mice. Male obese mice fed a high-fat diet (45% of calories from fat) were divided into two groups (n 13 each). One (FEN) received fenretinide (20 mg/kg body weight, intraperitoneally) and the other (O) received vehicle three times weekly for 24 d. C57BL/6J mice fed a normal-fat diet (16% of calories from fat) were used as a control (C; n 13). No changes in fat weight and serum leptin level could be observed in FEN mice. Lower plasma RBP4 was observed in FEN mice compared with O mice. Fenretinide improved whole-body insulin sensitivity based on glucose and insulin tolerance tests and the homeostasis model assessment of insulin resistance. Fenretinide decreased the plasma lipid (triglyceride, cholesterol, and free-fatty acid) levels, hepatic TG level, and histological steatosis score. The mechanism by which fenretinide prevents fatty liver may be explained by an increased plasma adiponectin level, increased activation of hepatic AMP-activated protein kinase, and the expression of peroxisome proliferator-activated protein-α and peroxisomal acyl-CoA oxidase, which promote fat oxidation. FEN alleviated insulin resistance and fatty liver in obese mice and thus may act as an anti-lipidemic and anti-diabetic drug.Key words fenretinide; retinol binding protein-4; insulin resistance; fatty liver; fatty acid oxidation Obesity is a worldwide public health problem and is associated with hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes, with insulin resistance being a common factor. The pathogenesis of these conditions occurs in insulin-acting peripheral tissues, including skeletal muscle, liver, and adipose tissue. [1][2][3] In particular, insulin resistance-related adipose tissue dysfunction leads to the release of a high level of free-fatty acids and perturbs the levels of various adipokines, such as leptin, adiponectin, and retinol binding protein 4 (RBP4), which directly or indirectly affect insulin sensitivity by modulating insulin signaling and molecules involved in glucose and lipid metabolism in many tissues. [4][5][6] RBP4 is a compact, globular, 21-kDa protein and was known only as a retinol carrier synthesized and secreted by the liver, until recently. 6) Although serum RBP4 originates largely from the liver under physiological conditions, it is secreted considerably from fat tissues in an insulin-resistant state.7) Yang et al. showed that adipose tissue-specific ablation of glucose transporter 4 increased RBP4 mRNA expression in adipocytes and serum RBP4 levels in rats, and focused on the link between the serum RBP4 level and insulin sensitivity. 8)Despite some reports that RBP4 is not associated with insulin resis...

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Nonalcoholic fatty liver disease is associated with hepatic and skeletal muscle insulin resistance in overweight adolescents

Abstract: An elevated IHTG content in overweight adolescents is associated with dyslipidemia and with insulin-resistant glucose metabolism in both liver and skeletal muscle.

Cited by 104 publications

References 43 publications

Non‐alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population‐based study

Non‐alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population‐based study

Metabolically normal obese people are protected from adverse effects following weight gain

Fenretinide Ameliorates Insulin Resistance and Fatty Liver in Obese Mice

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