AdipoRon prevents -thyroxine or isoproterenol-induced cardiac hypertrophy through regulating the AMPK-related pathway

Q: What are the key findings of this study?

AdipoRon significantly attenuated cardiac hypertrophy in rats, reducing diastolic interventricular septum thickness from 2.33±0.05 mm to 1.78±0.10 mm (p<0.01) in the isoprenaline model.

Q: What is the clinical evidence from this study?

Population: Isoprenaline (ISO) or L-thyroxine-induced cardiac hypertrophy in Sprague-Dawley rats (n=86). Intervention: AdipoRon vs. Vehicle control (0.5% carboxymethylcellulose sodium, 1 mg/kg/day intragastrically) co-administered with ISO or L-thyroxine. Primary outcome: Diastolic interventricular septum thickness (IVS;d, mm) in ISO-induced cardiac hypertrophy model at 30 days (p=<0.01).

Q: What does this research mean for the field?

AdipoRon attenuates isoprenaline- and l-thyroxine-induced cardiac hypertrophy and fibrosis in rats via activation of the AMPK-related signaling pathway. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Xinlei Hu; Qiong Ouyang; Lanlan Wang; Tingting Li; Xiaoxue Xie; Jun Liu

doi:10.1093/abbs/gmy152

November 5, 2018Acta Biochimica et Biophysica SinicaOpen Access

AdipoRon prevents -thyroxine or isoproterenol-induced cardiac hypertrophy through regulating the AMPK-related pathway

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Key result

AdipoRon reduces diastolic interventricular septum thickness by ~0.55 mm in rat cardiac hypertrophy models.

P<0.01
n=86

Why the study?

Cardiac hypertrophy is a risk factor for heart failure, and whether AdipoRon attenuates isoprenaline- or l-thyroxine-induced cardiac hypertrophy via the AMPK-related pathway was uncertain.

Does AdipoRon prevent isoprenaline- or L-thyroxine-induced cardiac hypertrophy and fibrosis via the AMPK-related pathway in Sprague-Dawley rats?

Structured PICO

Does AdipoRon prevent isoprenaline- or L-thyroxine-induced cardiac hypertrophy and fibrosis via the AMPK-related pathway in Sprague-Dawley rats?

P

Population

86 male Sprague-Dawley rats (250-300 g) with cardiac hypertrophy induced by isoprenaline (for 30 days) or L-thyroxine (for 10 days).

I

Intervention

AdipoRon (small molecule adiponectin receptor agonist) dissolved in 0.5% carboxymethylcellulose sodium (CMC-Na) administered intragastrically (i.g.) at 50 mg/kg/day for 30 days (co-administered with ISO 2.5 mg/kg/day i.p.) or at 50 mg/kg/day or 100 mg/kg/day for 10 days (co-administered with L-thyroxine 1 mg/kg/day i.p.).

C

Comparator

Model group receiving isoprenaline (ISO, 2.5 mg/kg/day i.p. for 30 days) or L-thyroxine (1 mg/kg/day i.p. for 10 days) plus vehicle (0.5% CMC-Na, 1 mg/kg/day i.g.); and healthy control group receiving saline (1 mg/kg/day i.p.) plus 0.5% CMC-Na (1 mg/kg/day i.g.).

O

Outcome

Cardiac hypertrophy assessed by heart weight/body weight (HW/BW) ratio, left ventricular weight/body weight (LV/BW) ratio, and echocardiographic parameters (including IVS;d, IVS;s, LVPW;d, LVPW;s, LVID, EF, FS, LV mass) at 30 days (ISO model) or 10 days (L-thyroxine model).surrogate

Main Result

Absolute Event Rate: 1.78% vs 2.33%

p-value: p=<0.01

This preclinical study provides initial evidence that the adiponectin receptor agonist AdipoRon attenuates β-adrenergic and thyroid hormone-induced cardiac hypertrophy and fibrosis in rats by activating the AMPK/PGC-1α/ERRα signaling pathway.

Limitations

Preclinical animal model (Sprague-Dawley rats); findings may not directly translate to human clinical populations.
Additional studies are needed to further understand the exact signaling pathways and whether other pathways beyond AMPK are involved.
Additional studies are needed to further understand the signaling pathway and how AdipoRon exerts its effects.
Future studies are required to determine whether other pathways are involved in this process.

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Implication

Hypothesis-generating for AdipoRon in hypertrophy; leaves open translation to human HF therapy.

Abstract

Cardiac hypertrophy is a risk factor which can intrigue heart failure. In the present study, we explored whether AdipoRon attenuates isoprenaline (ISO) or l-thyroxine-induced cardiac hypertrophy in Sprague-Dawley (SD) rats and whether the anti-hypertrophy effect is mediated by AMPK-related pathway. Here, cardiac hypertrophy was induced by injection of l-thyroxine or ISO in SD rats. In the treatment group, AdipoRon was co-administered. We examined the effects of AdipoRon on cardiac hypertrophy and hypertrophy signaling pathway. The weight of SD rats was recorded every day. Rats were killed for collection of blood and heart under anesthesia. The left heart weight and heart weight were weighed. Paraffin-embedded heart tissue regions (4 μm) were stained with hematoxylin and eosin or Masson to detect left heart hypertrophy and myocardial fibrosis. The serum BNP levels were determined by using an enzyme-linked immunosorbent assay. The mRNA levels of ANP, BNP, PGC-1α, and ERRα were evaluated by real-time PCR analysis. The protein expression levels of PGC-1α, ERRα, and pAMPK/AMPK were determined by western blot analysis. The results showed that AdipoRon significantly reversed heart weight (HW)/body weight (BW) ratio, left ventricular (LV)/BW ratio, serum BNP level and the mRNA level of ANP and BNP induced by ISO or l-thyroxine. ISO or l-thyroxine reduced both the mRNA level and protein level of ERRα and PGC-1α, and also reduced the protein level of pAMPK/AMPK. However, AdipoRon reversed ISO or l-thyroxine-induced changes of pAMPK/AMPK, ERRα, and PGC-1α. Our data indicated that the effects of AdipoRon are mediated partly by activating AMPK-related pathway, and AdipoRon plays a potential role in the prevention of cardiac hypertrophy.

Discussion

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Cite This Study

Hu et al. (2018) studied Isoprenaline (ISO) or L-thyroxine-induced cardiac hypertrophy in Sprague-Dawley rats (n=86). AdipoRon vs. Vehicle control (0.5% carboxymethylcellulose sodium, 1 mg/kg/day intragastrically) co-administered with ISO or L-thyroxine was evaluated on Diastolic interventricular septum thickness (IVS;d, mm) in ISO-induced cardiac hypertrophy model at 30 days (p=<0.01). AdipoRon significantly attenuated cardiac hypertrophy in rats, reducing diastolic interventricular septum thickness from 2.33±0.05 mm to 1.78±0.10 mm (p<0.01) in the isoprenaline model.

synapsesocial.com/papers/6a706925e36a167817e23015 https://doi.org/10.1093/abbs/gmy152

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AdipoRon prevents -thyroxine or isoproterenol-induced cardiac hypertrophy through regulating the AMPK-related pathway

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

AdipoRon prevents -thyroxine or isoproterenol-induced cardiac hypertrophy through regulating the AMPK-related pathway

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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