Original ArticleMetabolic profiling of serum from dogs with pituitary-dependent hyperadrenocorticism
Introduction
Hyperadrenocorticism (HAC) is one of the most common endocrine diseases in dogs, with an estimated prevalence of 0.27% to 1.46% (Carotenuto et al., 2019; O'Neill et al., 2016). HAC can be caused by an excessive cortisol production due to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor, namely pituitary-dependent HAC (PDH), or by a cortisol-secreting tumor arising in the adrenal cortex (Pérez-Alenza and Melián, 2017). The most common clinical signs consistently reported in both HAC types are polyuria, polydipsia and polyphagia, abdominal enlargement, and hepatomegaly (Ling et al., 1979; Reusch and Feldman, 1991).
Untargeted metabolomics allows a rapid and global description of many metabolites in a single sample, being of high interest to detect differences between physiological and pathological conditions (Emwas, 2015; Nicholson and Lindon, 2008). The number of studies carried out in veterinary medicine is small compared to humans (Carlos et al., 2020). However, the untargeted metabolomic analysis allowed the detection of metabolites that vary in dogs with diabetes compared to healthy animals (O'Kell et al., 2019). While, to the author's knowledge, metabolomics has not been applied to HAC in dogs. The analysis of the metabolic processes that occur in the serum can potentially help to understand the pathophysiological processes involved in a disease and it can also help to discover new biomarkers (Carlos et al., 2020). The importance of using reliable biomarkers in HAC patients (Hasenmajer et al., 2020; Ragnarsson, 2020) has been documented in humans and dogs (Jaffey et al., 2020). This study aimed to identify and compare differences in serum metabolites between dogs with PDH and healthy dogs.
Section snippets
Study Design and Case Selection
The individual characteristics of dogs enrolled in this study are presented in the supplementary information (Tables S1 and S2). These samples corresponded to two groups of dogs; one group of dogs diagnosed with PDH and one group of healthy dogs. Samples were collected between December 2018 and January 2020 and were stored at −80 °C until the analysis. In the case of dogs with PDH, the inclusion criteria were: (1) not presenting other pathology, (2) not having received treatment before
Metabolomics Analysis of Dogs With Pituitary-Dependent Hyperadrenocorticism and Healthy Dogs
A total of 314 different compounds were found in both groups. The different serum fingerprints between PDH and healthy dogs were shown in the PLS-DA model (R2 = 99%, Q2 = 41%, Fig. 1). Considering the screening of identified metabolites under the conditions of VIP > 1 and FC > 1.5 (Fig. 2), a total of 21 discriminative metabolites were found. Among them, two were identified, and 19 were recognized based on the Fragment Annotation Kit (FrAnK). This Django-based application implements Celery to
Discussion
This work describes alterations in serum metabolome that occur in dogs with PDH by applying metabolomics using a LC/MS analytical platform. A total of 21 metabolites showed significant alterations; 10 being downregulated and 11 being upregulated in the PDH group. The changes of higher magnitude were found in the fatty acids decanoic and arachidonic acid, and in the amino acids tryptophan and l-glutamine. In addition, alterations in phospholipids such as phosphatidylcholine (PC),
Conclusions
In conclusion, dogs with PDH showed alterations in the concentration of various metabolites compared to healthy dogs when serum was analyzed by LC/MS. The major variations were associated to arachidonic acid metabolism with the decrease of arachidonic acid and to glycerophospholipids metabolism with the decrease of PC(24:1(15Z)/14:1(9Z) and PI(18:0–20:4), and the increase of PE(20:0/16:1(9Z)). These metabolites could be related to insulin resistance and other complications (i.e. hypertension)
Acknowledgements
This research was supported by the European Structural and Investment Funds (Grant Agreement KK.01.1.16.0004). A.M.-P. was funded by Seneca Foundation through a post-doctoral grant (21239/PD/19). A.T. has a post-doctoral fellowships Ramón y Cajal (RYC-2017-22992) supported by the Ministerio de Economía y Competitividad, Agencia Estatal de Investigación (AEI), Spain, and The European Social Fund (ESF).er separation can be observed with the peak
References (38)
- et al.
Diagnosis of spontaneous hyperadrenocorticism in dogs. Part 1: pathophysiology, aetiology, clinical and clinicopathological features
Vet. J.
(2019) - et al.
Chronic non-invasive corticosterone administration abolishes the diurnal pattern of tph2 expression
Psychoneuroendocrinology
(2012) - et al.
Effects of dietary medium-chain triglyceride on weight loss and insulin sensitivity in a group of moderately overweight free-living type 2 diabetic Chinese subjects
Metab. Clin. Exp.
(2007) - et al.
The immune system in Cushing’s syndrome
Trends Endocrinol. Metab.
(2020) - et al.
Diagnostic contribution of individual components of adrenal function tests to diagnose canine hyperadrenocorticism
Vet. J.
(2020) - et al.
Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH
J. Hepatol.
(2008) - et al.
Concurrent hyperadrenocorticism and diabetes mellitus in dogs
Res. Vet. Sci.
(2017) - et al.
Medium chain fatty acid metabolism and energy expenditure: obesity treatment implications
Life Sci.
(1998) Cushing’s syndrome - disease monitoring: recurrence, surveillance with biomarkers or imaging studies
Best Pract. Res. Clin. Endocrinol. Metab.
(2020)- et al.
Endocrine hypertension in small animals
Vet. Clin. N. Am. Small Anim. Pract.
(2010)
Dietary saturated fat reduces alcoholic hepatotoxicity in rats by altering fatty acid metabolism and membrane composition
J. Nutr.
Fatty acid synthesis is indispensable for survival of human pluripotent stem cells
iScience
Dietary intake of medium- and long-chain triacylglycerols ameliorates insulin resistance in rats fed a high-fat diet
Nutrition
Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids
J. Lipid Res.
Capric acid as a potent dilator of canine vessels in vitro and in vivo
G. Pharmacol.: Vasc Syst.
Dendrobium officinale polysaccharide ameliorates the liver metabolism disorders of type II diabetic rats
Int. J. Biol. Macromol.
Ultrasonography criteria for differentiating ACTH dependency from ACTH independency in 47 dogs with hyperadrenocorticism and equivocal adrenal asymmetry
J. Vet. Intern. Med.
Canine metabolomics advances
Metabolomics
Cushing’s syndrome—an epidemiological study based on a canine population of 21,281 dogs
Open Vet. J.
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