Sains Malaysiana 51(6)(2022): 1821-1832

http://doi.org/10.17576/jsm-2022-5106-18

Comparison of Non-Alcoholic Fatty Liver Disease (NAFLD) Model using Diet-Induced Nafld Mice with Genetically Modified Mice

(Perbandingan Model Penyakit Hati Berlemak (NAFLD) menggunakan Tikus Nafld Diet-Teraruh dengan Tikus Terubah Suai secara Genetik)

MOHD DANIAL MOHD EFENDY GOON^1,2, SHARANIZA AB RAHIM³, NORMALA ABD LATIP⁴, MARDIANA ABDUL AZIZ⁵, NORIZAL MOHD NOOR⁵, LEW SOOK WEIH⁶, MUSALMAH MAZLAN³ & SITI HAMIMAH SHEIKH ABDUL KADIR^1,2,3,*

¹Institute of Molecular Medicine Biotechnology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia

²Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM), Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia

³Department of Biochemistry, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia

⁴Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Cawangan Selangor, 42300 Puncak Alam, Selangor Darul Ehsan, Malaysia

⁵Department of Pathology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia

⁶Department of Pediatrics, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia

Received: 11 August 2021/Accepted: 5 November 2021

ABSTRACT

Prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing steadily every year affecting all population both Western and Asian countries. The current treatments available for NAFLD are non-conclusive warranting newer effective pharmacological agents. Newly formulated agents require prior testing using animal models. However, in developing countries, these models are often costly. The possibility of using more affordable animal model in local settings should be investigated. In this study, ten Institute of Cancer Research (ICR) and seven B6.Cg-LepOb/J leptin-knockout (JAX) male mice were recruited. Five ICR and all JAX mice were subjected to high-fat diet (60% kcal fat) and remaining ICR mice were given standard diet (SD) for six weeks. Body weight and food intake were measured weekly while abdominal circumference, random blood glucose and liver span were measured at the end of the HFD study. Livers collected were subjected to histology assessment. Compared to ICR group, JAX group presented with significantly higher body weight (58 ± 0.72, p<0.05), larger body weight changes (16.57 ± 0.81, p<0.05), more HFD intake (197.14 ± 0.812, p<0.05) and larger abdominal circumference (11.79 ± 0.34: p<0.05). Liver from JAX group appeared with general steatosis and presentation of high-grade panacinar steatosis, low number of lobular inflammations and minimal fibrosis. Liver of ICR mice showed Zone 3 steatosis with high number of lobular inflammations without fibrosis. The NAFLD characteristics presented in JAX group suggested that B6.Cg-LepOb/J mice developed characteristics of NAFLD resembling human while ICR is suitable NAFLD model resembling human population resilient towards NAFLD.

Keywords: Animal model; B6.Cg-LepOb/J strain; high-fat diet; histology; Institute of Cancer Research strain; NAFLD

ABSTRAK

Kelaziman penyakit hati berlemak atau dikenali sebagai penyakit hati berlemak bukan alkohol (NAFLD) meningkat setiap tahun dalam kalangan populasi negara Barat dan Asia. Pada masa ini, rawatan bagi penyakit ini adalah tidak khusus, lalu mendorong kepada penyelidikan dalam mendapatkan agen rawatan yang berkesan. Rumusan agen rawatan yang baharu perlu dikaji menggunakan model haiwan. Penggunaan model haiwan dalam kalangan negara membangun membabitkan kos yang tinggi. Oleh itu, penyelidikan menggunakan model haiwan mengikut tetapan tempatan perlu dikaji. Dalam kajian ini, sepuluh ekor tikus jantan dan tujuh ekor tikus jantan B6.Cg-LepOb/J tanpa leptin (JAX) diambil daripada Institut Penyelidikan Kanser (ICR). Lima daripada tikus ICR dan kesemua tikus JAX diberi diet lemak tinggi (HFD) mengandungi 60% kcal daripada lemak selama enam minggu, dan selebihnya tikus ICR diberi diet piawai (SD). Berat badan dan pengambilan diet diukur setiap minggu manakala ukur lilit abdomen, bacaan glukosa darah rawak dan panjang hati diukur pada akhir tempoh kajian. Hati yang diperoleh daripada setiap tikus menjalani analisis histologi. Berbanding dengan kumpulan ICR, kumpulan JAX menunjukkan berat badan lebih berat (58 ± 0.72, p<0.05), perubahan berat badan lebih ketara (16.57 ± 0.81, p<0.05), pengambilan HFD lebih banyak (197.14 ± 0.812, p<0.05) dan ukur lilit abdomen lebih besar (11.79 ± 0.34: p<0.05). Analisis histologi kumpulan JAX menunjukkan kehadiran lemak (steatosis) dalam hati bertaraf tinggi, bilangan radang lobular dan parut yang rendah. Hati daripada kumpulan ICR menunjukkan gred 3 steatosis dan bilangan radang lobular yang tinggi. Ciri-ciri NAFLD yang ditonjolkan oleh kumpulan JAX menunjukkan model ini lebih mirip ke ciri-ciri NAFLD manusia manakala kumpulan ICR menunjukkan ciri-ciri ke arah manusia yang mempunyai kerintangan terhadap NAFLD.

Kata kunci: Diet lemak tinggi; histologi; model haiwan; NAFLD; strain B6.Cg-LepOb/J; strain Institut Penyelidikan Kanser

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^*Corresponding author; email: sitih587@uitm.edu.my