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http://doi.org/10.17576/jsm-2022-5107-01
Elucidating Hepatic
Lipidosis in Stray Cats through Serum Biochemistry, Liver Histopathology and Liver
RNA Expression of PPAR-δ and PPAR-γ
(Pengesanan Lipodesis Hepar pada Kucing Liar melalui Serum Biokimia, Histopatologi Hati dan Ekspresi RNA Hati PPAR- δ dan PPAR- γ)
1Department of Veterinary Preclinical Science, Faculty of Veterinary
Medicine, Universiti Putra Malaysia, 43400 UPM
Serdang, Selangor Darul Ehsan, Malaysia
2Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
3Department of Veterinary Pathology & Microbiology, Faculty of
Veterinary Medicine, Universiti Putra Malaysia, 43400
UPM Serdang, Selangor Darul Ehsan, Malaysia
4Institute of Biological Sciences, Faculty of Science, University of
Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
5Natural Medicines and Products Research Laboratory (NaturMeds), Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
6Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, 16100 Kota Bharu, Kelantan Darul Naim, Malaysia
7Jade
Hills Veterinary Hospital, Jade Hills, 43000 Kajang,
Selangor Darul Ehsan, Malaysia
8Beaty
Water Research Centre, Queen’s University, Kingston, Ontario, Canada
9School
of Environmental Studies & Department of Chemistry, Queen’s University,
Kingston, Ontario, Canada
Dataran Jade, 28, Jln Dataran Jls, 43000 K Dataran Jade, 28, Jln Dataran Jade 2,
Received: 10 October 2021/Accepted: 2 January 2022
ABSTRACT
Early
detection of feline hepatic lipidosis (FHL) with appropriate treatment can
increase prognosis significantly. This study looks into the serum biochemistry
and lipid composition of serum and liver samples in a group of stray cats
(N=18) collected from pounds in Klang Valley, Malaysia. Alanine aminotransferase
(ALT) in blood serum was used to detect for liver damage possibly due to FHL,
confirmed through light microscopy, serum biochemistry (triglyceride,
cholesterol, creatinine, and urea), liver triglyceride and cholesterol
concentrations, and liver RNA expression of lipid droplet regulators peroxisome
proliferator-activated receptors (PPARs). Differing severity of FHL in samples
were divided and grouped using an adapted scoring method observing fatty change
of liver (FCL) with trends between FCL groups investigated. Elevated serum ALT
reflective of increasing FCL severity was observed with elevated concentrations
of liver TAG and cholesterol levels. Serum TAG and cholesterol decreased with
heightened FCL pointing to fatty acid oxidation and lipid restoration in the
liver, supported by PPAR-γ expression which also propose macrophage
activation for liver recovery alongside PPAR-δ for lipogenesis and
inflammatory reactions. Elevated serum creatinine and urea levels with
increasing FCL severity propose overall intact hepatic function in the stray
cat samples.
Keywords: Felis catus;
hepatic lipidosis; PPAR-δ; PPAR-γ; serum biochemistry
Abstrak
Pengesanan awal lipidosis hepatik felin (LHF) berserta rawatan bersesuaian
dapat meningkatkan prognosis dengan ketara. Kajian ini meneliti serum biokimia
dan komposisi serum lipid dan sampel hati sekumpulan kucing liar (N=18) yang telah
dikumpul daripada pusat lindungan kucing terbiar di sekitar Lembah Klang,
Malaysia. Alanina aminotransferase (ALT) di dalam serum darah digunakan bagi
mengesan kerosakan hati yang mungkin disebabkan LHF, disahkan melalui
mikroskopi cahaya, serum biokimia (trigliserida, kolesterol, kreatinina dan
urea), kandungan trigliserida (TG) dan kolestrol hati serta pengekspresan asid
ribonukleik hati daripada pengatur titik lipid reseptor-reseptor
diaktifkan-pengproliferat peroksisom (RDPP) proliferator peroksisom -diaktifkan
reseptor (PPARs). Keparahan yang berbeza antara sampel LHF dibahagi dan
dikelompok menggunakan sebuah kaedah penilaian yang telah digubah untuk
memerhati perubahan lemak hati (PLH), seterusnya mengkaji trend PLH antara
kelompok. Kenaikan serum ALT seiring dengan keparahan PLH telah diperhati berserta
kenaikan kandungan TG dan kolesterol hati. Penurunan serum TG dan kolesterol
seiring dengan keparahan PLH menunjukkan berlakunya pengoksidaan asid lemak dan
pemulihan lipid di dalam hati, ini telah disokong oleh pengekspresan
RDPP-γ yang juga mencadangkan pengaktifan makrofaj bagi memulihkan hati di
samping RDPP-δ untuk lipogenesis dan reaksi-reaksi radang. Kenaikan
kreatinina dan serum urea seiring dengan keparahan PLH mencadangkan kebolehan
fungsi hepatik pada kucing-kucing terbiar yang dikaji.
Kata kunci: Felis catus; lipodesis hepar; PPAR-δ;
PPAR-γ; serum biokimia
REFERENCES
Armstrong, P.J. & Blanchard, G. 2009.
Hepatic lipidosis in cats. Veterinary Clinics of North America: Small Animal
Practice 39(3): 599-616.
Barmore, W.,
Azad, F. & Stone, W.L. 2020. Physiology, urea cycle. In StatPearls.
Treasure Island, Florida: StatPearls Publishing.
Baum, N., Dichoso,
C.C. & Carlton, C.E. 1975. Blood urea nitrogen and serum creatinine: Physiology
and interpretations. Urology 5(5): 583-588.
Bligh, E.G. & Dyer, W.J. 1959. A rapid
method of total lipid extraction and purification. Canadian Journal of
Biochemistry and Physiology 37(8): 911-917.
Boag, F., Weerakoon, J., Ginsburg, J., Havard,
C.W. & Dandona, P. 1985. Diminished creatinine
clearance in anorexia nervosa: Reversal with weight gain. Journal of
Clinical Pathology 38(11): 60-63.
Cárdenas, A. & Ginès,
P. 2009. A patient with cirrhosis and increasing creatinine level: What is it
and what to do? Clinical Gastroenterology and Hepatology 7(12): 1287-1291.
Center, S.A.
2007. Interpretation of liver enzymes. Veterinary Clinics of North America:
Small Animal Practice 37(2): 297-333.
Center, S.A.,
Crawford, M.A., Guida, L., Erb,
H.N. & King, J. 1993a. A retrospective study of 77 cats with severe hepatic
lipidosis: 1975-1990. Journal of Veterinary Internal Medicine 7(6): 349-359.
Cullen, J.M., van den Ingh,
T.S.G.A.M., Van Winkle, T., Charles, J.A. & Desmet,
V.J. 2006. Morphological classification of parenchymal disorders of the canine
and feline liver: 1. Normal histology, reversible hepatocytic injury and
hepatic amyloidosis. In WSAVA Standards for Clinical and Histological
Diagnosis of Canine and Feline Liver Diseases, edited by Rothuizen, J. Amsterdam: Elsevier. pp. 77-83.
de la Rosa Rodriguez, M.A. & Kersten,
S. 2017. Regulation of lipid droplet-associated proteins by peroxisome
proliferator-activated receptors. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology
of Lipids 1862(10): 1212-1220.
Delanaye, P.,
Cavalier, E. & Pottel, H. 2017. Serum creatinine:
Not so simple! Nephron 136: 302-308.
Dor, C., Adamany, J.L., Kisielewicz, C., de Brot, S., Erles, K. & Dhumeaux, M.P. 2018. Acquired urea cycle amino acid
deficiency and hyperammonaemic encephalopathy in a
cat with inflammatory bowel disease and chronic kidney disease. Journal of
Feline Medicine and Surgery Open Reports 4(2): 2055116918786750.
El-Gayar, S., Thüring-Nahler, H., Pfeilschifter,
J., Röllinghoff, M. & Bogdan, C. 2003. Translational
control of inducible nitric oxide synthase by IL-13 and arginine availability
in inflammatory macrophages. The Journal of Immunology 171(9): 4561-4568.
Farese, R.V.
& Walther, T.C. 2016. Lipid droplets go nuclear. Journal of Cell Biology 212(1): 7-8.
Glavind, E., Aagaard, N.K., Grønbæk, H., Møller, H.J., Orntoft, N.W., Vilstrup, H. & Thomsen, K.L. 2016. Alcoholic hepatitis
markedly decreases the capacity for urea synthesis. PLoS ONE 11(7): e0158388.
Hall, J.A., Barstad,
L.A. & Connor, W.E. 1997. Lipid composition of hepatic and adipose tissues
from normal cats and from cats with idiopathic hepatic lipidosis. Journal of
Veterinary Internal Medicine 11(4): 238-242.
Higgins, C. 2016. Urea and the Clinical Value of Measuring Blood Urea Concentration. https://acutecaretesting.org/en/articles/urea-and-the-clinical-value-of-measuring-blood-urea-concentration
Hinz, B.,
Phan, S.H., Thannickal, V.J., Galli, A., Bochaton-Piallat, M.L. & Gabbiani,
G. 2007. The myofibroblast: One function, multiple origins. American Journal
of Pathology 170(6): 1807-1816.
Kalaitzakis, E., Roubies, N., Panousis, N., Pourliotis, K., Kaldrymidou, E.
& Karatzias, H. 2007. Clinicopathologic evaluation
of hepatic lipidosis in periparturient dairy cattle. Journal of Veterinary
Internal Medicine 21(4): 835-845.
Kang, K., Reilly, S.M., Karabacak, V., Gangl, M.R., Hatano, B. & Lee, C. 2009. Adipocyte-dreved Th2 cytokines and myeloid PPAR delta. Cell
Metabolism 7(6): 485-495.
Kiapidou, S., Liava, C., Kalogirou, M., Akriviadis, E. & Sinakos, E.
2020. Chronic kidney disease in patients with non-alcoholic fatty liver
disease: What the hepatologist should know? Annals of Hepatology 19(2):
134-144.
Kuzi, S., Segev, G., Kedar, S., Yas, E. & Aroch, I. 2017.
Prognostic markers in feline hepatic lipidosis: A retrospective study of 71
cats. Veterinary Record 181(19): 512-512.
Lawler, D.F., Chase, K., Teckenbrock, R. & Lark, K.G. 2006. Heritable components
of feline hematology, clinical chemistry, and
acid-base profiles. Journal of Heredity 97(6): 549-554.
Ley, K.
2017. M1 means kill; M2 means heal. The Journal of Immunology 199(7):
2191-2193.
Liss,
K.H.H. & Finck, B.N. 2017. Biochimie PPARs and nonalcoholic fatty liver disease. Biochimie 136: 65-74.
Liu, J., Han, L., Zhu, L. & Yu, Y.
2016. Free fatty acids, not triglycerides, are associated with non-alcoholic
liver injury progression in high fat diet induced obese rats. Lipids in
Health and Disease 15(1): 1-9.
Mezey, E.
1982. Liver disease and protein needs. Annual Review of Nutrition 2(1):
21-50.
Minamoto, T., Walzem,
R.L., Hamilton, A.J., Hill, S.L., Payne, H.R., Lidbury,
J.A., Suchodolski, J.S. & Steiner, J.M. 2018.
Altered lipoprotein profiles in cats with hepatic lipidosis. Journal of
Feline Medicine and Surgery 21(4): 363-372.
Musso, G.,
Gambino, R., Tabibian, J.H., Ekstedt,
M., Kechagias, S., Hamaguchi,
M., Hultcrantz, R., Hagström,
H., Yoon, S.K., Charatcharoenwitthaya, P. &
George, J. 2014. Association of non-alcoholic fatty liver disease with chronic
kidney disease: A systematic review and meta-analysis. PLoS Medicine 11(7): e1001680.
Nakamura, M.T., Yudell, B.E. & Loor, J.J. 2014. Regulation of energy metabolism by
long-chain fatty acids. Progress in Lipid Research 53(1): 124-144.
Orecchioni, M., Ghosheh, Y., Pramod, A.B. & Ley, K. 2019. Macrophage
polarization: Different gene signatures in M1(LPS+) vs. classically and
M2(LPS-) vs. alternatively activated macrophages. Frontiers in Immunology 10: 1084.
Ostermann, M., Kashani,
K. & Forni, L.G. 2016. The two sides of
creatinine: Both as bad as each other? Journal of Thoracic Disease 8(7):
E628-E630.
Perrone, R.D., Madias,
N.E. & Levey, A.S. 1992. Serum creatinine as an index of renal function: New
insights into old concepts. Clinical Chemistry 38(10): 1933-1953.
Porta, C., Riboldi, E.,
Ippolito, A. & Sica, A. 2015. Molecular and
epigenetic basis of macrophage polarized activation. Seminars in Immunology 27(4): 237-248.
Shangraw, R.E.
& Jahoor, F. 1999. Effect of liver disease and transplantation
on urea synthesis in humans: Relationship to acid-base status. American
Journal of Physiology-Gastrointestinal and Liver Physiology 276(5): G1145-G1152.
Slack, A., Yeoman, A. & Wendon, J. 2010. Renal dysfunction in chronic liver
disease. Critical Care 14(2): 214.
Softic, S.,
Cohen, D.E. & Kahn, C.R. 2016. Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Digestive and Liver Disease 61(5): 1282-1293.
Takabatake, T., Ohta, H., Ishida, Y., Hara, H. & Ushiogi,
Y. 1989. Low serum creatinine levels in severe hepatic disease. Archives of
Internal Medicine 149(6): 1313-1315.
Tan, N.S., Vázquez-Carrera, M., Montagner,
A., Sng, M.K., Guillou, H.
& Wahli, W. 2016. Transcriptional control of
physiological and pathological processes by the nuclear receptor
PPARβ/δ. Progress in Lipid Research 64: 98-122.
Thongprayoon, C., Cheungpasitporn, W. & Kashani,
K. 2016. Serum creatinine level, a surrogate of muscle mass, predicts mortality
in critically ill patients. Journal of Thoracic Disease 8(5): E305-E311.
Valtolina, C.
& Favier, R.P. 2017. Feline hepatic lipidosis. Veterinary Clinics of
North America - Small Animal Practice 47(3): 683-702.
Washabau, R.J. &
Day, M.J. 2013. Canine and Feline
Gastroenterology. Amsterdam: Elsevier. pp. 1-1017.
Yerian, L.
2011. Histopathological evaluation of fatty and alcoholic liver diseases. Journal
of Digestive Diseases 12(1): 17-24.
Zawie, D.A.
& Garvey, M.S. 1984. Feline hepatic disease. The Veterinary Clinics of
North America. Small Animal Practice 14(6): 1201-1230.
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