Metabolic and morphometric changes in Indonesian cynomolgus monkeys (Macaca fascicularis) fed an atherogenic diet composed of locally sourced ingredients

Abstract

Background and Aim:This study was designed to determine the effects of a new atherogenic diet formulated at Institut Pertanian Bogor (IPB) (Bogor, Indonesia) on metabolic, morphometric, and carotid artery imaging of cynomolgus monkeys.Materials and Methods:A total of 20 adult male cynomolgus monkeys fed IPB-1 atherogenic diet for 1 year. Total plasma cholesterol (TPC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and morphometric measurements were evaluated at baseline and monthly during the study. Carotid plaques and intima-media thickness (IMT) were measured using ultrasonography at baseline and after 8 months of treatment.Results:This diet increased TPC, LDL, and TPC/HDL ratio and induced carotid atherosclerosis in this model. The TPC, LDL, and TPC/HDL ratio were positively associated; however, HDL was negatively associated with carotid plaques and IMT.Conclusion:The IPB-1 atherogenic diet formulated with locally and readily available ingredients provides an economically and scientifically feasible monkey model to study atherosclerosis in Indonesia and Southeast Asia.

Lesio Aterosklerosis pada Arteri Iliak Monyet Ekor Panjang sebagai Hewan Model Peripheral Arterial Disease (PAD)

“…Lipid darah, glukosa darah, dan morfometri tubuh diukur setiap bulan. Hasil evaluasi lipid darah selama perlakuan menunjukkan nilai total plasma kolesterol (TPK) yang bervariasi sehingga hewan coba dibagi ke dalam tiga kelompok, yaitu hipo-responsif (rata-rata TPK<200 mg/dl), intermediet responsif (rata-rata TPK 200-400 mg/dl), dan hiper-responsif (rata-rata TPK>400 mg/dl) (Laila et al, 2018). Total 9 ekor dari 20 ekor MEP kemudian dipilih menggunakan rancangan acak kelompok untuk dinekropsi (3 ekor mewakili tiap kelompok respons).…”

“…Kemunculan lesio aterosklerosis erat kaitannya dengan adanya berbagai faktor risiko. Laila et al (2018) telah mengamati munculnya faktor-faktor risiko akibat perlakuan pakan aterogenik IPB-1, di antaranya, indeks masa tubuh untuk menilai obesitas, kolesterol darah untuk menilai hiperkolesterolemia, dan glukosa darah untuk menilai diabetes. Semua monyet pada penelitian ini tidak mengalami obesitas.…”

“…Hal ini mirip dengan penelitian Clarkson et al (1988) di mana MEP yang diberi western diet (mengandung 0,35 mg/kal kolesterol) juga menunjukkan adanya kelompok yang hipo-responsif (TPK±220 mg/dl) dan hiper-responsif (TPK±420 mg/dl). Hal yang berbeda pada penelitian ini adalah hewan diberi pakan dengan kandungan kolesterol yang tidak terlalu tinggi, yaitu 0,28-0,29 mg/dl sehingga juga menginduksi respons menengah, yang kemudian dimasukkan ke dalam kelompok intermediet responsif (Laila et al, 2018).…”

Atherosclerotic Lesion of the Carotid Artery in Indonesian Cynomolgus Monkeys Receiving a Locally Sourced Atherogenic Diet

“…This diet can also be used for long-term feeding without inducing major complications in animals [ 8 ]. In a previous study, the IPB-1 atherogenic diet was able to induce hypercholesterolemia and increase the intima–media thickness surrounding the carotid artery, as clinically observed by ultrasound, in cynomolgus monkeys [ 9 ]. These results support conducting clinical research on atherosclerosis lesions without euthanizing the monkeys.…”

Recent Application of Zebrafish Models in Atherosclerosis Research

“…From the early 20th century to the era of new millennium, researchers have utilized a variety of animals in AS models for over 100 years, including rabbits, mice, rats, pigs and non-human primates ( Lee et al, 2017a ; Vedder et al, 2020 ). Large animal models such as pigs and non-human primates are suitable for AS research because their vascular lesion morphology and lipid metabolism are similar to that in humans ( Rapacz et al, 1986 ; Getz and Reardon, 2012 ; Laila et al, 2018 ). The disadvantages of these models include long modeling times, high cost, complex experimental procedures, and difficulties in obtaining large amounts of data ( Lee et al, 2017a ).…”