No Evidence of Ectopic Lipid Accumulation in the Pathophysiology of the Acromegalic Cardiomyopathy

Winhofer, Yvonne; Wolf, Peter; Krššák, Martin; Wolfsberger, Stefan; Tura, Andrea; Pacini, Giovanni; Gessl, Alois; Raber, Wolfgang; Kukurová, Ivica Just; Kautzky‐Willer, Alexandra; Knosp, Engelbert; Trattnig, Siegfried; Krebs, Michael; Luger, Anton

doi:10.1210/jc.2014-2242

Cited by 43 publications

(34 citation statements)

References 47 publications

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“…Our data confirm previously published results that indicate that subjects with ACRO have significantly lower HCL levels than healthy controls (1,2). In contrast to former studies, our controls were also matched for relative lean body mass in addition to being matched for sex, age, and BMI (1, 2).…”

Section: Discussionsupporting

confidence: 90%

“…In contrast to former studies, our controls were also matched for relative lean body mass in addition to being matched for sex, age, and BMI (1, 2). Median HCL levels in subjects with ACRO were 1.0% (ranging from 0.7% to 1.9%) and therefore were comparable to previously published mean HCL values in active ACRO of 1.2% and 2% (1,2). Median HCL values in controls were also similar to those reported in previously published studies, where mean HCL values ranged from 2.4% to 6%, (1,(12)(13)(14).…”

Section: Discussionsupporting

confidence: 89%

“…Acromegaly (ACRO) is characterized by a unique state of insulin resistance (IR), presumably due to the metabolic effects of increased growth hormone (GH) concentrations, which is associated with increased lipolysis and reduced total body fat. Recent studies have shown that hepatocellular lipid (HCL) content especially is significantly reduced in ACRO (1)(2)(3), which stands in contrast to ectopic lipid accumulation and nonalcoholic fatty liver disease (NAFLD) as prevalent attributes of IR in the general population (4)(5)(6). In murine models, supplementation of GH and insulin-like growth factor 1 (IGF1) improved mitochondrial function and reduced oxidative stress, de novo lipogenesis, and hepatic lipid uptake (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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Increased ATP synthesis might counteract hepatic lipid accumulation in acromegaly

Fellinger¹,

Wolf²,

Pfleger

et al. 2020

JCI Insight

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Increased ATP synthesis might counteract hepatic lipid accumulation in acromegaly

Fellinger¹,

Wolf²,

Pfleger

et al. 2020

JCI Insight

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“…Water infiltration observed in acromegaly (31) is secondary to increased sodium reabsorption due to overexpression of the epithelial sodium channel (ENaC) in distal tubules (32, 33) . By contrast with diabetes mellitus, where insulin resistance is associated with myocardial fat deposition (contributing to cardiac hypertrophy and dysfunction), a recent cardiac MRI study of patients with acromegaly showed that, despite insulin resistance, the lipid content of both the heart and liver was reduced (34) . Acromegalic cardiomyopathy can be slowed or prevented by suppressing GH and IGF1 oversecretion (2, 8, 35) .…”

Section: Discussionmentioning

confidence: 99%

Long-term effects of pegvisomant on comorbidities in patients with acromegaly: a retrospective single-center study

Kuhn¹,

Maione²,

Bouchachi³

et al. 2015

European Journal of Endocrinology

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ContextThe effect of pegvisomant on IGF1 levels in patients with acromegaly is well documented, but little is known of its long-term impact on comorbidity.AimThe aim of this retrospective study was to evaluate the effects of long-term pegvisomant therapy on cardiorespiratory and metabolic comorbidity in patients with acromegaly.Patients and methodsWe analyzed the long-term (up to 10 years) effect of pegvisomant therapy given alone (n=19, 45%) or in addition to somatostatin analogues and/or cabergoline (n=23, 55%) on echocardiographic, polysomnographic and metabolic parameters in respectively 42, 12 and 26 patients with acromegaly followed in Bicêtre hospital.ResultsAt the first cardiac evaluation, 20±16 months after pegvisomant introduction, IGF1 levels normalized in 29 (69%) of the 42 patients. The left ventricular ejection fraction (LVEF) improved significantly in patients whose basal LVEF was ≤60% and decreased in those whose LVEF was >70%. The left ventricular mass index (LVMi) decreased from 123±25 to 101±21 g/m2 (P<0.05) in the 17 patients with a basal LVMi higher than the median (91 g/m2), while it remained stable in the other patients. Pegvisomant reduced the apnoea–hypopnea index and cured obstructive sleep apnea (OSA) in four of the eight patients concerned. Long-term follow-up of 22 patients showed continuing improvements in cardiac parameters. The BMI and LDL cholesterol level increased minimally during pegvisomant therapy, and other lipid parameters were not modified.ConclusionsLong-term pegvisomant therapy not only normalizes IGF1 in a large proportion of patients but also improves cardiac and respiratory comorbidity.

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“…Pericardial fat (PERI) was assessed from T1 weighted ECG-gated cine true fast imaging with steady-state precession (TrueFISP) in four-chamber orientation in analogy to previously published methods [ 16 , 17 , 24 ]. Briefly, regions of interest were manually drawn along the borders of the fat surrounding the heart in three slices from the apex to the pulmonary trunk.…”

Section: Methodsmentioning

confidence: 99%

Pericardial- Rather than Intramyocardial Fat Is Independently Associated with Left Ventricular Systolic Heart Function in Metabolically Healthy Humans

et al. 2016

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BackgroundObesity is a major risk factor to develop heart failure, in part due to possible lipotoxic effects of increased intramyocardial (MYCL) and/or local or paracrine effects of pericardial (PERI) lipid accumulation. Recent evidence suggests that MYCL is highly dynamic and might rather be a surrogate marker for disturbed energy metabolism than the underlying cause of cardiac dysfunction. On the other hand, PERI might contribute directly by mechanic and paracrine effects. Therefore, we hypothesized that PERI rather than MYCL is associated with myocardial function.MethodsTo avoid potential confounding of metabolic disease 31 metabolically healthy subjects (age: 29±10yrs; BMI: 23±3kg/m2) were investigated using 1H-magnetic resonance spectroscopy and imaging. MYCL and PERI, as well as systolic and diastolic left ventricular heart function were assessed. Additionally, anthropometric data and parameters of glucose and lipid metabolism were analyzed. Correlation analysis was performed using Pearson’s correlation coefficient. Linear regression model was used to show individual effects of PERI and MYCL on myocardial functional parameters.ResultsCorrelation analysis with parameters of systolic heart function revealed significant associations for PERI (Stroke Volume (SV): R = -0.513 p = 0.001; CardiacIndex (CI): R = -0.442 p = 0.014), but not for MYCL (SV: R = -0.233; p = 0.207; CI: R = -0.130; p = 0.484). No significant correlations were found for E/A ratio as a parameter of diastolic heart function. In multiple regression analysis CI was negatively predicted by PERI, whereas no impact of MYCL was observed in direct comparison.ConclusionsCardiac fat depots impact left ventricular heart function in a metabolically healthy population. Direct comparison of different lipid stores revealed that PERI is a more important predictor than MYCL for altered myocardial function.

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No Evidence of Ectopic Lipid Accumulation in the Pathophysiology of the Acromegalic Cardiomyopathy

Cited by 43 publications

References 47 publications

Increased ATP synthesis might counteract hepatic lipid accumulation in acromegaly

Increased ATP synthesis might counteract hepatic lipid accumulation in acromegaly

Long-term effects of pegvisomant on comorbidities in patients with acromegaly: a retrospective single-center study

Pericardial- Rather than Intramyocardial Fat Is Independently Associated with Left Ventricular Systolic Heart Function in Metabolically Healthy Humans

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