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Observational Study
. 2025 May;41(4):e70049.
doi: 10.1002/dmrr.70049.

Could Ghrelin Expression Regulate Diastolic Cardiac Function in Type 2 Diabetic Obese Patients?

Celestino Sardu  1 , Nunzia D'Onofrio  2 , Maria Consiglia Trotta  2 , Maria Luisa Balestrieri  2 , Giovanni Francesco Nicoletti  3 , Giovanbattista D'Amico  1 , Carlo Fumagalli  1 , Carla Contaldi  4 , Giuseppe Pacileo  4 , Lucia Scisciola  1 , Maddalena Nicoletti  3 , Ludovica Vittoria Marfella  1 , Matilde Sbriscia  5 , Ferdinando Carlo Sasso  1 , Giuseppe Signoriello  6 , Giuseppe Paolisso  1   7 , Raffaele Marfella  1
Affiliations
Observational Study

Could Ghrelin Expression Regulate Diastolic Cardiac Function in Type 2 Diabetic Obese Patients?

Celestino Sardu et al. Diabetes Metab Res Rev. 2025 May.

Abstract

Aims: Adipose tissue expresses cytokines, sirtuin-1 (SIRT1), and microRNAs (miRs), regulating left ventricle (LV)-diastolic function (LV-DF). Ghrelin could modulate these pathways in patients with type 2 diabetes mellitus (T2DM) and obesity. We investigated ghrelin expression in T2DM obese patients after abdominal fat excision, and in those with LV-DF normalisation at 1 year of follow-up.

Materials and methods: Two-hundred and two T2DM obese patients enroled for abdominoplastic surgery were divided into those with normal LV-DF (group 1: E/E' < 9, n 76) and those with altered LV-DF: group 2 (9 < E/E' < 14; n 96) and group 3 (E/E' > 14, n 28).

Results: Patients with LV-diastolic dysfunction had over-inflammation, lower SIRT1 and higher abdominal fat sodium-glucose-transporter-two (SGLT2) expression (p < 0.05). They did not differ for ghrelin expression (p > 0.05). They evidenced different tissue/serum expression of miR-21, miR-92 and miR-126 (p < 0.05). Group 2 versus group 1 over-expressed tissue inflammatory markers and SGLT2 (p < 0.05), with higher extent in group 3 versus group 1 (p < 0.01) and versus group 2 (p < 0.025). SIRT1 was downregulated in group 2 versus group 1 (p < 0.05), and versus group 3 (p < 0.01). At the follow-up end, patients with lower LV-diastolic dysfunction had lower inflammation and SGLT2, and higher serum ghrelin (p < 0.05). They increased miR-126, and reduced serum miR-21 and miR-92 expression. At the follow-up end, 50 patients experienced LV-DF normalisation, which was predicted by tissue miR-126 (HR 1.344, CI 95% 1.126-1.937), and ghrelin (HR 1.123, CI 95% 1.016-1.310).

Conclusions: In T2DM obese patients, abdominal fat excision could reduce inflammation, up-regulating serum ghrelin and inducing miRs implied in LV-DF normalisation at 1 year of follow-up.

Clinical research trial number: NCT05988346.

Keywords: MicroRNA; SIRT1; abdominal fat; abdominoplasty; ghrelin; obesity; oxidative stress.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Ghrelin, SGLT2, sirtuins and inflammatory status content in abdominal fat. (A) Ghrelin, (B) SGLT2, (C) SIRT1, (D) TNF‐α, (E) IL‐8, (F) IL‐1β, (G) IL‐10, (H) IFN‐γ and (I) IL‐4 levels in abdominal fat specimens from diabetic obese patients of Group 1 (n = 80), Group 2 (n = 96) and Group 3 (n = 28) assessed by ELISA assay on homogenates. Data are reported as mean ± SD of n = 3 independent experiments. IFN‐γ, interferon gamma; IL‐10, interleukin 10; IL‐1β, interleukin 1 beta; IL‐4, interleukin 4; IL‐8, interleukin 8; SGLT2, sodium glucose transporter 2; SIRT1, sirtuin 1; TNF‐α, tumour necrosis alpha. *is for p < 0.05 versus Group 1; ** is for p < 0.01 versus Group 1.
FIGURE 2
FIGURE 2
Kaplan curves (lower part) for the cumulative risk to have the normalisation of LV diastolic function at 1 year of follow‐up in study cohorts divided for the different tertiles of fat ghrelin expression. E/E′: E wave/E′ wave ratio. The symbol * is for statistical significant (p < 0.05).
See this image and copyright information in PMC

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