ECE2023 Poster Presentations Diabetes, Obesity, Metabolism and Nutrition (159 abstracts)
Cabergoline counteracts adipose and skeletal muscle lipid accumulation through promoting oxidative pathway: an in vivo and in vitro preclinical study
Mariarosaria Negri 1 , Claudia Pivonello 2 , Feliciana Amatrudo 1 , Roberta Patalano 1 , Tatiana Montò 1 , Donatella Paola Provvisiero 1 , Chiara Simeoli 1 , Cristina de Angelis 1 , Renata Simona Auriemma 1 , Annamaria Colao 1,3 , Raffaella Crescenzo 4 & Rosario Pivonello 1,3
1Università Federico II di Napoli, Dipartimento di Medicina Clinica e Chirurgia, Naples, Italy; 2Università Federico II di Napoli, Dipartimento di Sanità Pubblica, Naples, Italy; 3Federico II University, UNESCO Chair for Health Education and Sustainable Development, Naples, Italy; 4Federico II University, Department of Biology, Task Force on Microbiome Studies, Naples, Italy
Obesity, characterized by an abnormal body fat accumulation mainly caused by a chronic imbalance between energy intake and expenditure, is a massive public health problem. Targeting excessive fat deposition in adipose tissue and ectopic fat accumulation in skeletal muscle through promoting lipid oxidation pathway may represent a promising strategy to counteract obesity. This study aims at investigating the effects of cabergoline (CAB), a dopamine agonist, on adipose and skeletal muscle tissues’ lipid accumulation by monitoring the protein levels of the main lipogenic markers in adipose tissue and by analyzing lipid oxidation pathway in both adipose and skeletal muscle tissues in in vivo and in vitro preclinical models. To this aim, 2 groups of 60-days aged male Wistar rats receiving a high-fat and fructose-rich diet for 28 days were analyzed: one receiving an oral dose of CAB 0.6 mg/kg of body weight every 3 days for a total duration of 2 weeks (HFFC), the other one receiving placebo (HFF). Moreover, in white adipocytes 3T3L1, lipid accumulation through Red Oil staining and oxidative pathway through WB analysis were performed after 3 days of CAB 10-10-10-6 M. HFFC visceral adipose tissues showed a significant decrease of PPARγ (P<0.05) and adiponectin (P<0.01) proteins, with a concomitant strong inhibition of leptin (60%) and FAS (75%) proteins compared to HFF. Moreover, HFFC visceral adipose tissues showed a significant reduction of pACC (P<0.05) and a strong increase in pAMPK Thr172 (74%) with a concomitant moderate stimulation of PKA catalytic subunit (PKA-Cα) (18%). Similarly, HFFC subcutaneous adipose tissues showed a significant decrease of leptin (P<0.01) and adiponectin (P<0.01) and a strong inhibition of PPARγ (70%) compared to HFF. Moreover, HFFC subcutaneous adipose tissues displayed a strong increase in pACC Ser72 (30%) associated with a significant stimulation of PKA-Cα (P<0.001) compared to HFF. Likewise, HFFC soleus tissues showed a significant increase in pACC Ser72 (P<0.05) associated with a significant stimulation of PKA-Cα (P<0.01) compared to HFF. Concomitantly, in white 3T3L1, Red Oil demonstrated that CAB 10-8M and 10-6M significantly inhibited lipid accumulation (P<0.001), while WB revealed that CAB 10-6M significantly stimulated pAMPK Thr172 (P<0.05) and slightly decreased PPARγ, leptin and FAS proteins compared to untreated 3T3L1. These preliminary preclinical data demonstrate a novel CAB lipolitic effect in murine adipose and muscle tissues mediated by oxidation pathway.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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