Obesity and sex influence insulin resistance and total and multimer adiponectin levels in adult neutered domestic shorthair client-owned cats.

In this study, we estimated insulin sensitivity and determined plasma concentrations of total-, low-molecular-weight (LMW), and high-molecular-weight (HMW) adiponectin and leptin in 72 domestic shorthair, neutered, client-owned cats. Glucose tolerance was assessed with an intravenous glucose tolerance test and body fat percentage (BF%) was measured with dual-energy x-ray absorptiometry. Total adiponectin was measured with 2 different ELISAs. Low-molecular-weight and HMW adiponectin plasma concentrations were determined by Western blot analysis after sucrose-gradient velocity centrifugation, and the adiponectin multimer ratio [SA = HMW/(HMW + LMW)] was calculated. Differences in glucose tolerance, leptin, total adiponectin, and multimer ratio among lean (BF% <35; n = 26), overweight (35 45; n = 18) cats as well as between male (n = 34) and female (n = 38) neutered cats were evaluated by linear regression and 2-way ANOVA. Sex and age were included as covariates for analysis of BF%, whereas BF%, fat mass, and lean body mass were covariates for analysis of sex differences. Increased BF% was negatively correlated with multimer ratio (SA, r = -45; P < 0.002), whereas no differences were found in total adiponectin concentrations among BF% groups (P > 0.01). Male cats had indices of decreased insulin tolerance and significantly lower total adiponectin concentrations than did female cats (mean ± SEM, 3.7 ± 0.4 vs 5.4 ± 0.5 µg/mL; P < 0.02). Altered SAs could contribute to an obesity-associated decreasing glucose tolerance in cats, and low total adiponectin concentrations may relate to increased risk of diabetes mellitus in neutered male cats.

Adiposity and adiponectin in dogs: investigation of causes of discrepant results between two studies.

Although one study showed lower adiponectin concentrations in obese dogs, other recent studies indicate that adiponectin might not be decreased in obese dogs, raising the possibility that the physiology of adiponectin is different in dogs than in humans. The aim of this study was to investigate possible causes of the discrepancy between the two largest studies to date that assessed the association between adiposity and adiponectin concentration in dogs, including the validity of the assay, laboratory error, and the effects of breed, sex, and neuter status on the relationship between adiposity and adiponectin concentrations. Adiponectin concentrations measured with a previously validated adiponectin ELISA were compared with those estimated by Western blotting analysis of reduced and denatured plasma samples. The possibility of laboratory error and the effect of EDTA anticoagulant and aprotinin were tested. Adiponectin concentration was measured by ELISA in 20 lean dogs (10 male and 10 female, 5 neutered in each sex). There was close correlation between adiponectin concentrations measured by ELISA and those estimated by Western blotting analysis (r = 0.90; P < 0.001). There was no substantial effect of EDTA, aprotinin, or laboratory error on the results. There was confounding by neuter status of the relationship between adiposity and adiponectin concentrations, but adiponectin concentrations were not significantly lower in male than in female lean dogs (females, 36 mg/L; males, 26 mg/L; P > 0.20) and were not significantly lower in intact than in neutered lean male dogs (intact, 28 mg/L; neutered, 23 mg/L; P = 0.49). We conclude that the adiponectin ELISA previously validated for use in dogs appears to be suitable for determination of canine adiponectin concentrations and that testosterone does not appear to have a strong effect on plasma adiponectin concentrations in dogs. Obesity might decrease adiponectin concentrations in intact but not in neutered dogs.

Distinct adiponectin profiles might contribute to differences in susceptibility to type 2 diabetes in dogs and humans.

Dogs develop obesity-associated insulin resistance but not type 2 diabetes mellitus. Low adiponectin is associated with progression to type 2 diabetes in obese humans. The aims of this study were to compare total and high molecular weight (HMW) adiponectin and the ratio of HMW to total adiponectin (S(A)) between dogs and humans and to examine whether total or HMW adiponectin or both are associated with insulin resistance in naturally occurring obese dogs. We compared adiponectin profiles between 10 lean dogs and 10 lean humans and between 6 lean dogs and 6 age- and sex-matched, client-owned obese dogs. Total adiponectin was measured with assays validated in each species. We measured S(A) with velocity centrifugation on sucrose gradients. The effect of total and HMW adiponectin concentrations on MINMOD-estimated insulin sensitivity was assessed with linear regression. Lean dogs had total and HMW adiponectin concentrations three to four times higher than lean humans (total: dogs 32 ± 5.6 mg/L, humans 10 ± 1.3 mg/L, P<0.001; HMW: dogs 25 ± 4.5 mg/L, humans 6 ± 1.3 mg/L, P<0.001) and a higher S(A) (dogs: 0.78 ± 0.05; humans: 0.54 ± 0.08, P = 0.002). Adiponectin concentrations and S(A) were not lower in obese dogs (0.76 ± 0.05 in both groups; P=1). Total adiponectin, HMW adiponectin, and S(A) were not associated with insulin sensitivity in dogs. We propose that differences in adiponectin profiles between humans and dogs might contribute to the propensity of humans but not dogs to develop type 2 diabetes. Dogs with chronic, naturally occurring obesity do not have selectively reduced HMW adiponectin, and adiponectin does not appear to be important in the development of canine obesity-associated insulin resistance.

Synergistic effects of ascorbic acid and thiazolidinedione on secretion of high molecular weight adiponectin from human adipocytes.

AIM: To test the hypothesis that ascorbic acid (AA) and thiazolidinedione (TZD) would have additive effects on HMW adiponectin secretion by virtue of different modes of action. METHODS: We determined the effects of supplementation of AA and/or TZD on expression and secretion of total and HMW adiponectin from human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes in the absence or presence of the proinflammatory cytokine TNFα. RESULTS: AA supplementation significantly increased secretion of HMW adiponectin (1.7-fold) without altering adiponectin expression or total adiponectin secretion. TZD significantly increased expression (3-fold) and secretion of total (1.4-fold) but not HMW adiponectin. Combined supplementation resulted in a significant increase in expression (3-fold) and secretion of total (1.8-fold) and HMW (5-fold) adiponectin. Similar results were seen in cells co-treated with TNFα. CONCLUSIONS: These data show that AA and TZD have synergistic rather than simple additive effects on secretion of HMW adiponectin from human adipocytes and raise the possibility that differences in AA levels may contribute to the variability in adiponectin multimer profiles and efficacy of TZD in humans. Our results also provide a rationale for longitudinal clinical trials investigating the effects of AA supplementation with or without TZD on adiponectin and metabolic profiles.

How pure is your thiosialoside? A reinvestigation into the HPLC purification of thioglycosides of N-acetylneuraminic acid.

The synthesis of thiosialosides as potential biological probes for investigations involving the use of sialic acid-recognising proteins has been reinvestigated. It has been found that the most efficient method for the preparation of thiosialosides free from any 2,3-didehydro sialic acid contaminants involves an intermediate HPLC purification of thiosialosides as their methyl esters. Subsequent methyl ester hydrolysis provides thiosialosides (eg. 6 and 14) which are suitable for studies involving the use of sialic acid-recognising proteins.

Carcinogenicity studies in animals relevant to the use of anabolic agents in animal production.

It has long been known that certain estrogens and testosterone may increase, or sometime decrease, the incidence of neoplasmas in laboratory animals. They probably act by switching-on inappropriate genetic information or switching-off appropriate genetic information contained in nucleic acids. For instance, they may switch-on in adult animals information which is relevant only to a certain stage of embryogenesis or they may facilitate the expression of oncogenic viruses which would otherwise lay harmlessly dormant. The situation is rendered complex because an effect on one endocrine gland leads to effects on others so that factors which favour tumour development may result indirectly from administration of an anabolic or other hormonal agent. Two kinds of neoplasm are now known to be associated with human exposure to anabolic agents: vaginal adenocarcinoma and liver-cell tumours. Tumours of both kinds are among the spectrum of neoplasms that has been seen in laboratory animals exposed to agents of the same kind. In both animals and man there is evidence that tumours arising in response to anabolic agents are sometimes, initially at least, hormone-dependent. The evidence that 17beta-estradiol, diethylstilbestrol, chlormadinone, and testosterone are carcinogenic for laboratory animals is briefly reviewed and the reader's attention is directed towards the 1974 IARC Monograph on the evaluation of sex hormones for carcinogenic risk to man where the same evidence is reviewed more extensively. The significance for man of the results of studies on laboratory animals is discussed with special reference to the use of anabolic agents in meat production. Non-residue uses are to be preferred, as are naturally-occurring agents as opposed to compounds which do not occur in nature. More information is needed concerning the possible effects of prolonged exposure to very low doses of anabolic agents.

Nontraumatic determination of left ventricular ejection fraction by radionuclide angiocardiography.

Previous reports have suggested that left ventricular ejection fraction can be assessed by recording the passage of peripherally administered radioactive bolus through the heart. The accuracy and validity of this technique were examined in 20 patients undergoing diagnostic cardiac catheterization. 99m-Tc-human serum albumin was injected via a central venous catheter into the superior vena cava and precordial activity recorded with a gamma scintillation camera interfaced to a small digital computer. A computer program was designed to generate time-activity curves from the left ventricular blood pool and to calculate left ventricular ejection fractions from the cyclic fluctuations of the left ventricular time-activity curve which correspond to left ventricular volume changes during each cardiac cycle. The results correlated well with those obtained by biplane cineangiocardiography (r equals 0.94) and indicated that the technique should allow accurate and reproducible determination of left ventricular ejection fraction. The findings, however, demonstrated that the time-activity curve must be generated from a region-of-interest which fits the left ventricular blood pool precisely and must be corrected for contributions arising from noncardiac background structures. This nontraumatic and potentially noninvasive technique appears particularly useful for serial evaluation of the acutely ill patient and for follow-up studies in nonhospitalized patients.