Short‐term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated

Johnson, Nathan A.; Stannard, Stephen R.; Rowlands, David S.; Chapman, Phil; Thompson, Campbell; Sachinwalla, Toos; Thompson, Martin W.

doi:10.1111/j.1464-5491.2006.01952.x

Cited by 7 publications

(9 citation statements)

References 49 publications

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“…Previously, Busetto et al [34] have noted a reduction in liver size 8 weeks after gastric banding; hepatic lipid Table 3). IMCL lipid content correlates with insulin sensitivity [35], and short-term starvation is associated with IMCL accumulation [36,37]. No reduction in IMCL lipid during weight loss on hypocaloric diet was observed [24], and likewise, no lowering of soleus muscle fat was found in type 2 diabetes after weight reduction [27].…”

Section: Discussionmentioning

confidence: 94%

Lipid Mobilization Following Roux-en-Y Gastric Bypass Examined by Magnetic Resonance Imaging and Spectroscopy

et al. 2008

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RYGBP causes rapid lipid mobilization from visceral and subcutaneous adipose depots and enhanced free fatty acid flux to the liver. An exceptional disconnection between liver fat and insulin sensitivity occurs in the early dynamic phase after surgery. However, in the late phase, the energy restriction imposed by the surgical procedure also reduces the liver lipids, but not the intramyocellular lipids.

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Section: Discussionmentioning

confidence: 94%

Lipid Mobilization Following Roux-en-Y Gastric Bypass Examined by Magnetic Resonance Imaging and Spectroscopy

et al. 2008

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“…Four of the six studies assessing the vastus lateralis muscle found a significant increase of IMF after a high-fat diet intervention ( 9 , 20 , 35 , 39 ). These studies implemented a 54–83% fat diet in their experimental conditions.…”

Section: Resultsmentioning

confidence: 99%

The Effects of Diet on the Proportion of Intramuscular Fat in Human Muscle: A Systematic Review and Meta-analysis

Ahmed

Singh²,

Khattab

et al. 2018

Front. Nutr.

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BackgroundThere is an increasing trend in the consumption of poor-quality diets worldwide, contributing to the increase of non-communicable diseases. Diet directly influences physiological composition and subsequently physical health. Studies have shown that dietary macronutrient and energy content can influence the proportion of intramuscular fat (IMF), which mediates various metabolic and endocrine dysfunction. The purpose of this systematic review was to identify evidence in the literature assessing the association between different dietary interventions on the proportion of IMF in humans.MethodsThree medical databases were investigated (Medline, EMBASE, and Cochrane) to identify studies assessing changes in IMF after dietary interventions. The primary outcome measure was the change in IMF proportions after a dietary intervention. The effects of high-fat, high-carbohydrate, low-calorie, and starvation diets were assessed qualitatively. A meta-analysis assessing the effect of high-fat diets was conducted. Follow-up sensitivity and subgroup analyses were also conducted.ResultsOne thousand eight hundred and sixty-six articles were identified for review. Of these articles, 13 were eligible for inclusion after a full screening. High-fat diets increased IMF proportions, standardized mean difference = 1.24 (95% confidence interval, 0.43–2.05) and a significant overall effect size (P = 0.003). Diets with an increased proportion of carbohydrates decreased IMF proportions; however, increasing caloric intake with carbohydrates increased IMF. Starvation diets increased IMF stores, and hypocaloric diets did not result in any IMF proportion changes.ConclusionThis systematic review suggests that high-fat diets and diets with caloric intake increased above the amount required to maintain BMI with carbohydrates, and short-term starvation diets are associated with increases in IMF content. Further studies are needed to assess the effects of macronutrient combinations on IMF and the influence of diet-induced IMF alterations on health outcomes. In addition, IMF poses a possibly effective clinical marker of health.

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“…The use of circulating NEFA as a biomarker is limited by evidence suggesting that plasma NEFA sampled downstream from the site of NEFA uptake does not necessarily predict intracellular NEFA accumulation. Clinical experiments have shown that excessive plasma NEFAs are not required for hypertriglyceridemia to provoke insulin resistance (33), and suppressing NEFA does not reverse insulin resistance when intracellular fatty acids remain elevated (34).…”

Section: Discussionmentioning

confidence: 99%

Antisense-Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes

et al. 2016

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OBJECTIVETo determine the effects of volanesorsen (ISIS 304801), a second-generation 2'-O-methoxyethyl chimeric antisense inhibitor of apolipoprotein (apo)C-III, on triglyceride (TG) levels and insulin resistance in patients with type 2 diabetes. RESEARCH DESIGN AND METHODSA randomized, double-blind, placebo-controlled trial was performed in 15 adult patients with type 2 diabetes (HbA 1c >7.5% [58 mmol/mol]) and hypertriglyceridemia (TG >200 and <500 mg/dL). Patients were randomized 2:1 to receive volanesorsen 300 mg or placebo for a total of 15 subcutaneous weekly doses. Glucose handling and insulin sensitivity were measured before and after treatment using a two-step hyperinsulinemic-euglycemic clamp procedure. RESULTSTreatment with volanesorsen significantly reduced plasma apoC-III (288%, P = 0.02) and TG (269%, P = 0.02) levels and raised HDL cholesterol (HDL-C) (42%, P = 0.03) compared with placebo. These changes were accompanied by a 57% improvement in whole-body insulin sensitivity (P < 0.001). Importantly, we found a strong relationship between enhanced insulin sensitivity and both plasma apoC-III (r = 20.61, P = 0.03) and TG (r = 20.68, P = 0.01) suppression. Improved insulin sensitivity was sufficient to significantly lower glycated albumin (21.7%, P = 0.034) and fructosamine (238.7 mmol/L, P = 0.045) at the end of dosing and HbA 1c (20.44% [24.9 mmol/mol], P = 0.025) 3 months postdosing. CONCLUSIONSVolanesorsen reduced plasma apoC-III and TG while raising HDL-C levels. Importantly, glucose disposal, insulin sensitivity, and integrative markers of diabetes also improved in these patients after short-term treatment.Insulin resistance states usually seen in the context of obesity and type 2 diabetes are commonly associated with a metabolic dyslipidemia that amplifies cardiovascular disease risk. Among patients with type 2 diabetes, insulin resistance impairs the ability to utilize glucose as fuel, prompting a switch toward fat storage that promotes free fatty acid flux, hepatic triglyceride (TG) synthesis, and secretion of large VLDL particles (1). Cholesteryl ester transfer protein-mediated exchange of

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Short‐term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated

Cited by 7 publications

References 49 publications

Lipid Mobilization Following Roux-en-Y Gastric Bypass Examined by Magnetic Resonance Imaging and Spectroscopy

Lipid Mobilization Following Roux-en-Y Gastric Bypass Examined by Magnetic Resonance Imaging and Spectroscopy

The Effects of Diet on the Proportion of Intramuscular Fat in Human Muscle: A Systematic Review and Meta-analysis

Antisense-Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes

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