Metabolic disorders and inflammation in obese dogs, cats, horses and cattle

Pretilost je jedan od najvećih zdravstvenih problema današnjice, kako u ljudi tako i udomaćenih životinja. Procjenjuje se kako je više od 50 % pasa, mačaka i konja pretilo. Pretilost je bolest sama po sebi te je ujedno uzrok i faktor rizika za razvoj mnogih drugih oboljenja kao što su kardio-pulmonarne bolesti, poremećaji lokomotornog sustava, kronične upale, dijabetes i metabolički sindrom. Pretilost utječe na životni vijek i kvalitetu života oboljelih životinja, a u ovom radu uspoređuju se razlike u metaboličkom odgovoru pasa, mačaka, konja i goveda. Cilj rada je prikazati i usporediti najučestalije metaboličke posljedice pretilosti (inzulinska rezistencija, dijabetes, metabolički sindrom i kronična upala). Adipozno tkivo najveći je endokrini organ, proizvodi mnoge različite molekule koje kontroliraju metabolizam, imuni odgovor, diferencijaciju i upalu. Glavni hormoni su adiponektin i leptin koji kontroliraju metabolizam masti i ugljikohidrata te su izravno povezani s razvojem inzulin- ske rezistencije i dijabetesa. Uspoređujući njihove koncentracije u promatranim životinjama može se zaključiti kako su vrijednosti leptina uvijek više u pretilih individua, dok su koncentracije adiponektina niže nego u zdravoj populaciji. Inzulinska rezistencija česta je u svih pretilih životinja, no metabolizam različitih životinjskih vrsta reagira drugačije. Inzulin rezistentne mačke s vremenom će razviti dijabetes, dok se u pasa i konja neće razviti. U goveda inzulinska re- zistencija ne utječe na metabolizam masti, a zbog proizvodnje mlijeka koncentracije glukoze bit će u referentnom intervalu. Pretilost je glavni faktor rizika za razvoj dijabetesa, no samo će mačke razviti dijabetes tipa 2 koji je izravno povezan s pretilosti. Psi rijetko obolijevaju od dijabetesa, a u pravilu je to uvijek dijabetes tipa 1. U humanoj medicini velika se pozornost posvetila istraživanju metaboličkog sindroma, njegovim uzrocima i posljedicama. Posljednjih desetljeća slične su promjene i stanja uočene i u kućnih ljubimaca i farmskih životinja te su definirani metabolički sindromi nalik humanima. Mačke razvijaju sindrom najsličniji humanom, samo bez dodatnog kardiološkog rizika. Psi pate od inzulinske rezistencije, hiperlipide- mije i hiperglikemije, imaju blagu hipertenziju, a ponekad i strukturne promjene srca, no još uvijek nije moguće ustvrditi izravnu povezanost kardioloških promjena i pretilosti. Konji obolijevaju od prelaminitičkog metaboličkog sindroma gdje su prekomjerna težina i inzulinska rezistencija glavni uzroci laminitisa. Metabolički sindrom goveda (Fat cow syndrome) primijećen je u prekondicioniranih goveda tijekom peripartuma. Sindrom obuhvaća inzulinsku rezistenciju, ketozu i hepatičku lipidozu, promjene u imunosnom odgovoru te povećanu sklonost infekcijama. Adipozno tkivo sadrži adipocite i makrofage, tipove stanica koji mogu proizvoditi proupalne molekule. Povećanje adipoznog tkiva vodi do velike infiltracije makrofaga u rastuće tkivo, gdje uzrokuju upalu koja se može dokazati i procijeniti mjerenjem citokina i proteina. Zbog niskih koncentracija proupalnih molekula i bez prikladnih analitičkih testova i dalje je teško definirati ulogu upale u pretilosti. Većina se znanstvenika slaže da su koncentracije markera upale, interleukin-6, tumor nekrotični faktor α i C-reaktivni protein povišene u odnosu na zdrave pojedince normalne težine te definiraju pretilost kao kronično upalno stanje.Obesity is a major health problem today, both in humans and in domesticated animals. It is estimated that over 50% of all dogs, cats and horses are obese. Obesity itself is a disease, and it is a cause and risk factor for many other severe conditions and illnesses, such as cardio-pulmonary diseases, locomotor disorders, chronic inflammation, diabetes, and metabolic syndrome. All obese animals have a shorter life expectancy and poorer quality of life. This study compared the differences in metabolic response to obesity between dogs, cats, horses and cattle. Insulin resistance, diabetes, metabolic syndrome, and chronic inflammation are well known metabolic consequences of excessive body weight, and therefore are the focus of the study. Adipose tissue is the largest endocrine organ, producing many different molecules that control metabolism, immune response, differentiation and inflammation. The main hormones are adiponectin and leptin, which control fat and sugar metabolism and are therefore directly associated with developing insulin resistance and diabetes. Comparing their concentrations in the observed animals, it was concluded that leptin values were always higher and that adiponectin values were lower in obese subjects than in healthy subjects. Insulin resistance is common in all obese animals, though the metabolic response varies. Insulin resistant cats will eventually develop diabetes, while dogs and horses will not. In cattle, insulin resistance does not affect fat metabolism, and due to milk production, glucose concentrations are within the reference range. Obesity is the main risk factor for developing diabetes, though only cats will develop type two diabetes, which is directly associated with excessive weight, while dogs rarely develop diabetes, and if they do it is type one diabetes. In human medicine, a great deal of attention has been given to metabolic syndrome, its causes and consequences. In recent decades, similar changes and conditions have been observed in domesticated animals, and variations of metabolic syndromes have been defined. Cats develop syndromes similar to humans, though without the additional cardiac risk. Dogs suffer from insulin resistance, hyperlipidaemia, hyperglycaemia and hypertension, and possibly structural changes in the heart, though it is still not possible to establish a direct connection between cardiac conditions and obesity. Equine metabolic syndrome or prelaminitic metabolic syndrome is defined in horses where obesity and insulin resistance are the main risk factors for developing laminitis. Fat cow syndrome is seen in over-conditioned cattle during peripartum. This syndrome includes insulin resistance, ketosis, hepatic lipidosis and changes in the immune response, causing cattle to become prone to infection. Adipose tissue contains adipocytes and macrophages, and both cell types can produce pro-inflammatory molecules. Weight gain will lead to massive macrophage infiltration into tissue, causing inflammation that can be estimated and quantified through the measurement of inflammatory cytokines and proteins. Due to the low concentrations of proinflammatory molecules, and without appropriate tests, it is still difficult to define the role of inflammation in obesity. Most researchers agree that several markers, particularly interleukin-6, tumour necrosis factor α and C-reactive protein, are indeed higher than in healthy non-obese individuals, thereby defining obesity as a chronic inflammatory condition