Intramyocellular lipid accumulation and reduced whole  body lipid oxidation in HIV lipodystrophy

Luzi, Livio; Perseghin, Gianluca; Tambussi, Giuseppe; Meneghini, Elena; Scifo, Paola; Pagliato, E; Maschio, Alessandro Del; Testolin, G.; Lazzarin, Adriano

doi:10.1152/ajpendo.00391.2001

Cited by 71 publications

(52 citation statements)

References 42 publications

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“…The observation that in obese women [5] and type 2 diabetic patients [7] the impairment of fat oxidation was not reversed by considerable body weight reduction and that it was also detected in individuals with impaired glucose tolerance [8] would support the hypothesis of a primary genetic defect. An impairment of fasting lipid oxidation in association with insulin resistance and IMCL accumulation may also be seen as a secondary consequence of metabolic disturbances [9]. The reverse metabolic picture was described by our group in healthy humans in whom, despite a moderate degree of overweight, insulin sensitivity and normal IMCL content were preserved in association with higher fasting lipid oxidation [10].…”

Section: Introductionmentioning

confidence: 73%

Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients

Lattuada¹,

Costantino²,

Caumo³

et al. 2005

Diabetologia

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Aims/hypothesis: Intramyocellular lipid accumulation and insulin resistance are thought to be due to reduced lipid oxidation in a human model of high risk of developing type 2 diabetes. Methods: We studied 32 offspring of type 2 diabetic parents and 32 control individuals by means of DXA, indirect calorimetry, insulin clamp and 1 H MRS of the calf muscles, and differences between and within study groups were analysed before and after segregation by quartiles of fasting lipid oxidation. Results: In comparison with control subjects, the offspring showed impaired insulin sensitivity, which was associated with higher fasting intramyocellular lipid content (Spearman's rho −0.35; p=0.04), but fasting lipid oxidation did not differ between groups (1.21±0.46 vs. 1.25±0.37 mg·kg −1 lean body mass per min; p=0.70). Nevertheless, offspring in the lowest quartile of lipid oxidation had the most severe impairment of insulin sensitivity and a strong association was shown between lipid oxidation and insulin sensitivity within quartiles (Spearman's rho 0.47; p=0.01); this was not observed within the control group (Spearman's rho 0.13; p=0.47). Intramyocellular lipid content was not significantly different within quartiles of lipid oxidation in either of the groups. Conclusions/interpretation: Insulin sensitivity improved across increasing quartiles of fasting lipid oxidation in the offspring group, but remained constant in the control group, supporting the hypothesis that impaired fat oxidation is a primary pathogenic factor of insulin resistance in people with a genetic background for type 2 diabetes. Despite their association with impaired insulin sensitivity, soleus and tibialis anterior intramyocellular lipid content remained constant across increasing quartiles of fasting lipid oxidation within both groups.

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Section: Introductionmentioning

confidence: 73%

Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients

Lattuada¹,

Costantino²,

Caumo³

et al. 2005

Diabetologia

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“…The causes of this clinical picture are still not completely defined. The lipodystrophy in HIV-1 patients in antiretroviral treatment is associated with peripheral fat wasting and central adiposity, dyslipidemia, and insulin resistance but also with increase intramuscular fat accumulation, related to development of the insulin resistance syndrome [2] .…”

Section: Human Immunodeficiency Virus (Hiv)mentioning

confidence: 99%

Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy?

Benedini

Luzi

2016

Journal of Translational Internal Medicine

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Recently new evidence about fibroblast growth factor 21 (FGF21) highlights the opportunities to use this molecule in new pharmaceutical formulations to combat type 2 diabetes and metabolic syndrome. It is well known that HIV is per se a condition of insulin resistance and in particular the patient with HIV-related lipodystrophy has a condition strictly related to metabolic syndrome. Lipodystrophy is associated with severe metabolic side effects, including dyslipidemia, hepatic insulin resistance, and lipid oxidation impairment. Research carried out showed that FGF21 levels were significantly increased in untreated HIV-1-infected patients and the increase was much marked in HIV-1-infected antiretroviral-treated patients that have developed lipodystrophy and in the patients with greatest metabolic alterations. FGF21 is expressed mainly by the liver, but also by other tissues such as the thymus, adipose tissue, and skeletal muscle. Therefore, many researchers have considered the investigation of possible variations of FGF21 in patients with significant alterations in body composition both in regard to fat mass and lean mass. In the light of the possible interactions between FGF21 and metabolic syndrome, it seems interesting to evaluate the implication of this hormone in patients with HIV-related lipodystrophy who have a severe metabolic picture of insulin resistance with important alterations in body composition.

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“…Insulin resistance precedes type 2 diabetes and the connection between hepatic steatosis and insulin resistance has been established in many individual experimental settings. Nonetheless, a causal relationship between hepatic lipid accumulation and insulin resistance (IR) remains to be established (Pan et al, 1997;Gavrilova et al, 2000;Lewis et al, 2002;Luzi et al, 2003).…”

Section: A Impaired Insulin Signaling and Reduced Insulin Sensitivitmentioning

confidence: 99%

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

Anderson

Borlak²

2008

Pharmacol Rev

341

255

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Intramyocellular lipid accumulation and reduced whole body lipid oxidation in HIV lipodystrophy

Cited by 71 publications

References 42 publications

Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients

Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients

Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy?

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

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