Impact of hyperlipidaemia on intermediary metabolism, faecal microbial metabolites and urinary characteristics of lipoprotein lipase deficient vs. normal cats
Hyperlipidaemia has been hypothesised to affect several metabolic pathways. For instance, it has been proposed that hyperlipidaemia and enhanced lactate dehydrogenase (LDH) activity might increase hepatic oxalate (Ox) synthesis (Schmiedl et al., 2000), which may be relevant for calcium oxalate (CaOx) urolith formation. In humans, individuals with calcium oxalate monohydrate–calcium oxalate dihydrate (COM‐COD) stones had higher blood triglyceride concentrations than control patients without urinary stones (Inci, Demirtas, Sarli, Akinsal, & Baydilli, 2012). In another study in rats serving as a model for human metabolic syndrome, hyperlipidaemia was accompanied by increased renal calcium (Ca) excretion, a lower urine pH and reduced renal citrate excretion (Iba et al., 2010). Taken together, they represent potential risk factors for the development of urinary CaOx precipitates. CaOx urinary stones are also a common problem in cats, representing 40%–63% of all feline uroliths (Cannon, Westropp, Ruby, & Kass, 2007; Gerber, Brandenberger‐Schenk, Rothenanger, & Müller, 2016; Hesse, Orzekowsky, Frenk, & Neiger, 2012; Houston & Moore, 2009; Houston, Vanstone, Moore, Weese, & Weese, 2016; Osborne, Lulich, Kruger, Ulrich, & Koehler, 2009; Rogers et al., 2011). However, a possible association between hyperlipidaemia and stone formation has not been investigated to date. It was the hypothesis of this study that renal Ox excretion is increased in cats with hyperlipidaemia when compared with normal cats, resulting in a higher risk for CaOx urolith formation. To test this hypothesis, lipoprotein lipase (LPL)‐deficient cats were used. The LPL deficiency results from a mutation in the LPL gene by a substitution of arginine for glycine at residue 412 (Ginzinger et al., 1996). Affected cats are hyperlipidaemic, independent of dietary interventions or secondary diseases.
The impact of hyperlipidaemia on endogenous Ox synthesis and urine characteristics aside, disorders in lipid metabolism may also affect gut microbiota. Hyperlipidaemic mice affected by metabolic syndrome showed changes in the composition of the intestinal microbiota compared to healthy mice, potentially mediated by an impaired function of the innate immune system (Vijay‐Kumar et al., 2010). Conversely, recent data in hyperlipidaemic rats indicate that modification of the gut microbiota after probiotic treatment could benefit lipid metabolism by decreasing serum lipids (Chen et al., 2014). In general, hyperlipidaemia represents an abnormal state in the organism, resulting from a dysregulation in lipid metabolism (Hassing et al., 2012). It can therefore be hypothesised that hyperlipidaemia could act as an endogenous stressor for the host in an acute or chronic manner. In this context, an effect of stress on the intestinal microbiota has been reported, potentially mediated by modifications in neurotransmitter release and cytokine secretion (Cresci & Bawden, 2015; Konturek, Brzozowski, & Konturek, 2011). To date, the composition and activity of the intestinal microbiota have not been reported in hyperlipidaemic cats. In this study, it was hypothesised that the activity of the gut microbiota differed in the LPL‐deficient cats compared to normal controls, possibly induced by long‐term hyperlipidaemia and associated chronic stress for the host.