Hepatic lipid accumulation is associated with multiple metabolic pathway alterations but not dyslipidemia and insulin resistance in central bearded dragons (Pogona vitticeps).

OBJECTIVE: To investigate associations between hepatic fat accumulation, fibrosis, and plasma values of primary metabolites, biochemical measurands, insulin, and lipoproteins in bearded dragons. ANIMALS: 48 adult central bearded dragons (Pogona vitticeps). METHODS: Dragons were sedated with alfaxalone, and a blood sample was collected. Plasma was submitted for untargeted primary metabolomics using gas chromatography time-of-flight mass spectrometry, a biochemistry panel, and a lipoprotein panel determined by PAGE. Hepatic lipid content was quantified by liver attenuation measurements from CT images and digital image analysis of standardized histologic sections of the liver. Fibrosis was quantified by digital image analysis on Masson's trichrome-stained histologic sections. Severity was determined from pathologic review of liver sections according to a standardized grading system. Statistical associations were investigated using serial linear models adjusted for false discovery rate and multivariate statistics. RESULTS: Both hepatic fat and fibrosis had a significant effect on CT liver attenuation values. Several oligosaccharides (maltotriose, maltose, ribose, trehalose) and alkaline phosphatase were significantly and linearly increased with hepatic lipid content (all q < .05). On partial least square-discriminant analysis, ß-hydroxybutyric acid was the most important discriminatory variable between fatty liver severity grades on histology. No significant associations were found with insulin, lipoproteins, and succinic acid. CLINICAL RELEVANCE: Bearded dragons with hepatic lipid accumulation experienced multiple metabolic pathway disruptions, some being compatible with mitochondrial dysfunction. No evidence of insulin resistance or dyslipidemia was found. Hepatic biopsy and histopathology remain recommended for reliably diagnosing and staging fatty liver disease in bearded dragons.

Feeding dogs a high-fat diet induces metabolic changes similar to natural aging, including dyslipidemia, hyperinsulinemia, and peripheral insulin resistance.

OBJECTIVE: The goal of this study was to characterize changes induced by a high-fat diet in body composition, insulin levels and sensitivity, blood lipids, and other key biomarkers also associated with the metabolic dysfunction that occurs with natural aging. ANIMALS: 24 male Beagle dogs, 3 to 7 years of age, of mixed castration status. METHODS: Dogs were randomly assigned to continue twice daily feeding of the commercial adult maintenance diet (n = 12, including 2 intact) that they were previously fed or to a high-fat diet (12, including 2 intact) for 17 weeks between December 1, 2021, and April 28, 2022. Assessments included body composition (weight, body condition score, and adipose mass determined by deuterium enrichment), clinical chemistries, plasma fatty acid quantification, oral glucose tolerance test, and histology of subcutaneous and visceral adipose biopsy samples. RESULTS: The high-fat diet led to increased body weight, body condition score, fat mass and adipocyte size, hyperinsulinemia and peripheral insulin resistance, and elevations in serum lipids, including cholesterol, triglycerides, and several species of free fatty acids. Leptin levels increased in dogs fed a high-fat diet but not in control dogs. There were no significant changes in routine clinical chemistry values in either group. CLINICAL RELEVANCE: Feeding a high-fat diet for 17 weeks led to potentially deleterious changes in metabolism similar to those seen in natural aging in dogs, including hyperinsulinemia, insulin resistance, and dyslipidemia. A high-fat diet model may provide insights into the similar metabolic dysfunction that occurs during natural aging.

Lipolysis inhibition as a treatment of clinical ketosis in dairy cows: A randomized clinical trial.

Excessive and protracted lipolysis in adipose tissues of dairy cows is a major risk factor for clinical ketosis (CK). This metabolic disease is common in postpartum cows when lipolysis provides fatty acids as an energy substrate to offset negative energy balance. Lipolysis in cows can be induced by the canonical (hormonally induced) and inflammatory pathways. Current treatments for CK focus on improving glucose in blood (i.e., oral propylene glycol [PG], or i.v. dextrose). However, these therapies do not inhibit the canonical and inflammatory lipolytic pathways. Niacin (NIA) can reduce activation of the canonical pathway. Blocking inflammatory responses with cyclooxygenase inhibitors such as flunixin meglumine (FM) can inhibit inflammatory lipolytic activity. The objective of this study was to determine the effects of including NIA and FM in the standard PG treatment for postpartum CK on circulating concentrations of ketone bodies. A 4-group, parallel, individually randomized trial was conducted in multiparous Jersey cows (n = 80) from a commercial dairy in Michigan during a 7-mo period. Eligible cows had CK symptoms (lethargy, depressed appetite, and milk yield) and hyperketonemia (blood ß-hydroxybutyrate [BHB] ≥1.2 mmol/L). Cows with CK were randomly assigned to 1 of 3 groups where the first group received 310 g of oral PG once per day for 5 d; the second group received PG for 5 d + 24 g of oral NIA once per day for 3 d (PGNIA); and the third group received PG for 5 d + NIA for 3 d + 1.1 mg/kg i.v. FM once per day for 3 d (PGNIAFM). The control group consisted of cows that were clinically healthy (HC; untreated; BHB <1.2 mmol/L, n = 27) matching for parity and DIM with all 3 groups. Animals were sampled at enrollment (d 0), and d 3, 7, and 14 to evaluate ketone bodies and circulating metabolic and inflammatory biomarkers. Effects of treatment, sampling day, and their interactions were evaluated using mixed effects models. Logistic regression was used to calculate the odds ratio (OR) of returning to normoketonemia (BHB <1.2 mmol/L). Compared with HC, enrolled CK cows exhibited higher blood concentrations of dyslipidemia markers, including nonesterified fatty acids (NEFA) and BHB, and lower glucose and insulin levels. Cows with CK also had increased levels of biomarkers of pain (substance P), inflammation, including lipopolysaccharide-binding protein, haptoglobin, and serum amyloid A, and proinflammatory cytokines IL-4, MCP-1, MIP-1α, and TNFα. Importantly, 72.2% of CK cows presented endotoxemia and had higher circulating bacterial DNA compared with HC. By d 7, the percentage of cows with normoketonemia were higher in PGNIAFM = 87.5%, compared with PG = 58.33%, and PGNIA = 62.5%. At d 7 the OR for normoketonemia in PGNIAFM cows were 1.5 (95% CI, 1.03-2.17) and 1.4 (95% CI, 0.99-1.97) relative to PG and PGNIA, respectively. At d 3, 7, and 14, PGNIAFM cows presented the lowest values of BHB (PG = 1.36; PGNIA = 1.24; PGNIAFM = 0.89 ± 0.13 mmol/L), NEFA (PG = 0.58; PGNIA = 0.59; PGNIAFM = 0.45 ± 0.02 mmol/L), and acute phase proteins. Cows in PGNIAFM also presented the highest blood glucose increment across time points and insulin by d 7. These data provide evidence that bacteremia or endotoxemia, systemic inflammation, and pain may play a crucial role in CK pathogenesis. Additionally, targeting lipolysis and inflammation with NIA and FM during CK effectively reduces dyslipidemia biomarkers, improves glycemia, and improves overall clinical recovery.

Dyslipidemia induced by lipid diet in late gestation donor impact on growth kinetics and in vitro potential differentiation of umbilical cord Wharton's Jelly mesenchymal stem cells in goats.

Mesenchymal stem cells (MSC) from the umbilical cord (UC) have several attractive properties for clinical use. This study aimed to verify the impact of a lipid-rich diet during late gestation of donor goats on the growth and differentiation of MSCs from UC. From the 100th day of pregnancy to delivery, 22 goats were grouped based on their diet into the donor-lipid (DLD; n = 11) and donor-baseline (DBD; n = 11) diet groups. Diets were isonitrogenous and isoenergetic, differing in fat content (2.8% vs. 6.3% on a dry matter basis). Wharton's jelly (WJ) fragments were cultured. After primary culture, samples of WJ-MSCs were characterized by the expression of CD90, CD73, CD34, CD45, CD105, and Fas genes, mitochondrial activity using MitoTracker (MT) fluorescence probe, and growth kinetics. Population doubling time (PDT) was also determined. WJ-MSCs were differentiated into chondrocytes, adipocytes and osteocytes, and the mineralized area and adipocytes were determined. The lipid diet significantly increased triglyceride and cholesterol levels during pregnancy. The DLD group showed sub-expression of the CD90 gene, a high MT intensity, and a low proliferation rate at the end of the subculture. The mean PDT was 83.9 ± 1.3 h. Mineralized area and lipid droplet stain intensity from osteogenic and adipogenic differentiations, respectively, were greater in DLD. We conclude that in donor goats, dietary dyslipidemia during late pregnancy affects the ability of UC-derived MSCs to express their developmental potential in vitro, thus limiting their possible use for therapeutic purposes.

Energy hormone response to fasting-induced dyslipidemia in obese and non-obese donkeys.

Metabolic and endocrine disorders, such as dyslipidemia, are common in donkeys. Negative energy balance due to fasting, stressful conditions, or disease is a major trigger for fat mobilization often leading to dyslipidemia. The hormonal response to fasting has not been well characterized in donkeys. Therefore, this work aimed to study variations in insulin, glucagon, leptin, total adiponectin, ghrelin, and insulin-like growth factor-1 concentrations, insulin-to-glucagon (IGR) and glucagon-to-insulin (GIR) molar ratios, and lipid and carbohydrate parameters during a 66 h fasting period in 8 adult donkeys, and to determine differences depending on body condition. Obese donkeys developed earlier lipid mobilization (increased plasma total triglyceride and total cholesterol concentrations) compared to non-obese donkeys. Plasma glucose and leptin concentrations decreased in obese animals. After 60 h fasting, obese donkeys showed a significant increase in glucagon and decrease in leptin. GIR significantly increased, while insulin and IGR decreased in both groups. These findings support faster lipid mobilization in response to negative energy status in obese donkeys during fasting, which could be linked to greater glucagonemia and could explain the predisposition of these animals to dyslipidemia.

The plasma lipidome of the Quaker parrot (Myiopsitta monachus).

Dyslipidemias and lipid-accumulation disorders are common in captive parrots, in particular in Quaker parrots. Currently available diagnostic tests only measure a fraction of blood lipids and have overall problematic cross-species applicability. Comprehensively analyzing lipids in the plasma of parrots is the first step to better understand their lipid metabolism in health and disease, as well as to explore new lipid biomarkers. The plasma lipidome of 12 Quaker parrots was investigated using UHPLC-MS/MS with both targeted and untargeted methods. Targeted methods on 6 replicates measured 432 lipids comprised of sterol, cholesterol ester, bile acid, fatty acid, acylcarnitine, glycerolipid, glycerophospholipid, and sphingolipid panels. For untargeted lipidomics, precursor ion mass-to-charge ratios were matched to corresponding lipids using the LIPIDMAPS structure database and LipidBlast at the sum composition or acyl species level of information. Sterol lipids and glycerophospholipids constituted the majority of plasma lipids on a molar basis. The most common lipids detected with the targeted methods included free cholesterol, CE(18:2), CE(20:4) for sterol lipids; PC(36:2), PC(34:2), PC(34:1) for glycerophospholipids; TG(52:3), TG(54:4), TG(54:5), TG(52:2) for glycerolipids; SM(d18:1/16:0) for sphingolipids; and palmitic acid for fatty acyls. Over a thousand different lipid species were detected by untargeted lipidomics. Sex differences in the plasma lipidome were observed using heatmaps, principal component analysis, and discriminant analysis. This report presents the first comprehensive database of plasma lipid species in psittacine birds and paves the way for further research into blood lipid diagnostics and the impact of diet, diseases, and drugs on the parrot plasma lipidome.

Dietary supplementation of brown seaweed (Sargassum latifolium) alleviates the environmental heat stress-induced toxicity in male Barki sheep (Ovis aries).

Heat stress (HS) is the most potent environmental stressors for livestock in tropical and subtropical regions. HS induced splanchnic tissue hypoxia and intestinal oxidative damage, leading to endotoxemia and systemic inflammation. The present study evaluated and compared the modulatory effects of feeding Barki male sheep (Ovis aries) on a standard concentrated diet containing 2% or 4% of the brown seaweed (Sargassum latifolium) followed by roughage for 40 consecutive days on the toxicity-induced by exposure to severe environmental HS (temperature-humidity index = 28.55 ± 1.62). The present study showed that the diet containing Sargassum latifolium (especially 4%) modulated significantly (P < 0.05-0.001) almost all changes shown in the HS-exposed sheep including the increase in the thermo-respiratory responses (skin and rectal temperatures, and respiration rate) and the resulted dyslipidemia, anemia, and systemic inflammation (blood leukocytosis, the elevation in the erythrocyte sedimentation rate, and the increase in serum proinflammatory cytokines and heat shock protein-70 concentrations). In addition, Sargassum latifolium improved significantly (P < 0.05-0.001) the body-weight gain, kidney functions (especially at the high dose), and blood antioxidant defense system (total antioxidant capacity, and the activities of catalase and superoxide dismutase) in the HS-exposed sheep, as well as protected the animals from oxidative tissue damage and the risk of atherosclerosis. In conclusion, feeding sheep with the diet containing 4% of Sargassum latifolium was safe and suitable for animal nutrition, as well as efficiently alleviated the harmful effects of the environmental HS in Barki sheep through improving the animal antioxidant defense system, and regulating the thermo-respiratory and inflammatory responses.

Hypocholesterolemia in cats: a multicenter retrospective study of 106 cats.

OBJECTIVES: The aim of this study was to describe the clinicopathologic findings and associated diseases found in a population of hypocholesterolemic cats referred to two tertiary care facilities. METHODS: An electronic medical record search was performed at two veterinary university referral centers to identify cats with serum cholesterol values below the reference interval between January 2004 and 2016. Clinicopathologic data were reviewed for each case and cats were classified into specific disease categories based on clinical diagnosis. Median cholesterol values were compared between disease categories, as well as between survivors and non-survivors. RESULTS: In total, 106 hypocholesterolemic cats were included. The median age of the cats was 6 years (range 0.24-18 years). The most common disease categories were gastrointestinal (25.9%), hepatobiliary (19.8%), hematologic (14.8%) and urogenital (14.8%). Though median serum cholesterol values did not differ significantly between survivors and non-survivors, cats with concurrent hypoalbuminemia were at higher risk (odds ratio 15.6, 95% confidence interval 5.2-46.6; P <0.0001) of not surviving to discharge than cats with normal serum albumin concentrations. CONCLUSIONS AND RELEVANCE: Taken together, our data suggest that while the degree of hypocholesterolemia did not appear to influence survival rates, the concurrent presence of hypocholesterolemia and hypoalbuminemia was associated with a worse prognosis.

Lipidograma e sensibilidade à insulina em éguas Mangalarga Marchador / Lipidogram and insulin sensitivity in Mangalarga Marchador mares

A dislipidemia é um achado comum, porém não determinante, na síndrome metabólica equina (SME). O objetivo do presente trabalho foi caracterizar a dislipidemia em animais obesos com risco de SME. Para isso, 18 éguas foram alocadas em grupos, de acordo com escore corporal (EC) de 1 a 9: no grupo ideal, animais com EC de 4,5 a 5,5 (n= 6), no grupo sobrepeso, com EC de 6 a 7 (n= 6) e no grupo obeso, animais com EC de 7,5 a 9 (n= 6). Coletaram-se amostras de sangue em jejum de concentrado para determinação de triglicerídeos, colesterol total, glicemia e concentração de insulina. Valores preditivos de sensibilidade à insulina (RISQI) e de secreção ß-pancreática (MIRG) foram calculados. O grupo obeso apresentou níveis maiores em relação aos outros grupos de triglicerídeos (P=0,001) e acima do ideal em concentrações de colesterol (P=0,012). Não foi observada diferença nas concentrações plasmáticas de glicose (P=0,53), de insulina (P=0,10) ou de RISQI (P=0,46). Houve diferença entre os grupos nos valores de MIRG (P=0,048), tendo o grupo obeso obtido resultados maiores quando comparado com o grupo ideal. O aumento do EC foi associado ao aumento das concentrações plasmáticas de colesterol e triglicerídeos, o que caracteriza um estado de dislipidemia e de elevação da secreção das células ß-pancreáticas.(AU)

Increased indicators of fat metabolites are found in Equine Metabolic Syndrome (EMS) subjects, although these parameters are not included in the EMS definition described in the literature and in its diagnosis. The objective of this study was to characterize dyslipidemia in obese insulin resistant mares. 18 mares were allocated in three groups according to body condition score (BCS) in a 1 to 9 scale. In the Ideal group there were animals with BCS 4.5 to 5.5 (n= 6), in the Overweight group, the BCS were 6 to 7 (n= 6), and in the Obese group (n= 6), BCS 7.5 to 9. Concentrate fasting blood samples were taken to determine triglycerides, total cholesterol, glucose, and insulin concentrations in plasma. Insulin sensitivity proxy (RISQI) and ß-pancreatic secretion proxy (MIRG) were calculated from glucose and insulin data. The Obese group had higher triglyceride levels (P= 0.001), compared to other groups, and higher total cholesterol compared to the Ideal Group (P= 0.012). No differences in plasma glucose (P= 0.53), insulin (P= 0.10) concentrations and insulin sensitivity (RISQI: P= 0.463) were seen among groups. The Obese Group had a higher ß-pancreatic secretion (MIRG: P= 0.048) compared to the Ideal Group. The increased BCS was related to the plasma fat metabolites a higher ß-pancreatic secretion.(AU)

APOB-associated cholesterol deficiency in Holstein cattle is not a simple recessive disease.

In 2015, cholesterol deficiency (CD) was reported for the first time as a new recessive defect in Holstein cattle. After GWAS mapping and identification of a disease-associated haplotype, a causative loss-of-function variant in APOB was identified. CD-clinically affected APOB homozygotes showed poor development, intermittent diarrhea and hypocholesterolemia and, consequently, a limited life expectation. Herein, we present a collection of 18 cases clinically diagnosed as CD-affected APOB heterozygotes. CD-clinically affected heterozygotes show reduced cholesterol and triglyceride blood concentrations. The differences in total blood cholesterol and triglycerides between nine CD-clinically affected and 36 non-affected heterozygotes were significant. As only some APOB heterozygotes show the clinical CD phenotype, we assume that the penetrance is reduced in heterozygotes compared to the fully penetrant effect observed in homozygotes. We conclude that APOB-associated CD represents most likely an incomplete dominant inherited metabolic disease with incomplete penetrance in heterozygotes.

The Burmese cat as a genetic model of type 2 diabetes in humans.

The recent extension of genetic tools to the domestic cat, together with the serendipitous consequences of selective breeding, have been essential to the study of the genetic diseases that affect them. Cats are increasingly presented for veterinary surveillance and share many of human's heritable diseases, allowing them to serve as natural models of these conditions. Feline diabetes mellitus is a common condition in domestic cats that bears close pathological and clinical resemblance to type 2 diabetes in humans, including pancreatic ß-cell dysfunction and peripheral insulin resistance. In Australia, New Zealand and Europe, diabetes mellitus is almost four times more common in cats of the Burmese breed than in other breeds. This geographically based breed predisposition parallels familial and population clustering of type 2 diabetes in humans. As a genetically isolated population, the Australian Burmese breed provides a spontaneous, naturally occurring genetic model of type 2 diabetes. Genetically isolated populations typically exhibit extended linkage disequilibrium and increased opportunity for deleterious variants to reach high frequencies over many generations due to genetic drift. Studying complex diseases in such populations allows for tighter control of confounding factors including environmental heterogeneity, allelic frequencies and population stratification. The homogeneous genetic background of Australian Burmese cats may provide a unique opportunity to either refine genetic signals previously associated with type 2 diabetes or identify new risk factors for this disease.

Prognostic value of dyslipidemia for sick dogs hospitalized in the intensive care unit of a veterinary teaching hospital.

OBJECTIVE To evaluate the lipidemia status and serum concentrations of cholesterol and triglycerides of dogs when initially examined for hospitalization in the intensive care unit (ICU) of a veterinary teaching hospital and to determine whether these variables were predictive of survival to hospital discharge. DESIGN Retrospective cohort study. ANIMALS 549 client-owned sick (n = 398) and healthy (151) dogs. PROCEDURES Medical records of sick dogs hospitalized in the ICU at a veterinary teaching hospital between January 1, 2012, and September 30, 2015, and of healthy dogs evaluated at the teaching hospital during the same time frame were reviewed. Data collection included signalment, results of initial physical and clinicopathologic examinations, treatments, diagnosis, and survival to hospital discharge. Lipidemia status and serum concentrations of cholesterol and triglycerides were compared between healthy and sick dogs and between sick dogs that did and did not survive to hospital discharge. Regression analysis was performed to determine whether these variables were predictive of survival to hospital discharge in dogs. RESULTS Factors associated with increased odds of sick dogs not surviving to hospital discharge were hypocholesterolemia (OR, 1.87; 95% confidence interval [CI], 1.04 to 3.34), hypertriglyceridemia (OR, 3.20; 95% CI, 2.00 to 5.13), and concurrent hypocholesterolemia and hypertriglyceridemia (OR, 55.7; 95% CI, 3.2 to 959.6) at the time of initial evaluation. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that hypocholesterolemia and hypertriglyceridemia, alone or in combination, at initial examination were negative prognostic indicators for survival of dogs hospitalized in the ICU and that these conditions were easily identified with routine serum clinicopathologic analyses. (J Am Vet Med Assoc 2019;254:699-709).

Gentiopicroside Ameliorates Diabetic Peripheral Neuropathy by Modulating PPAR- Γ/AMPK/ACC Signaling Pathway.

BACKGROUND/AIMS: Gentiopicroside is promising as an important secoiridoid compound against pain. The present study aimed to investigate the analgesic effect and the probable mechanism of Gentiopicroside on Diabetic Peripheral Neuropathy (DPN), and to figure out the association among Gentiopicroside, dyslipidemia and PPAR- γ/AMPK/ACC signaling pathway. METHODS: DPN rat models were established by streptozotocin and RSC96 cells were cultured. Hot, cold and mechanical tactile allodynia were conducted. Blood lipids, nerve blood flow, Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity (SNCV) were detected. Gene and protein expression of PPAR- γ/AMPK/ACC pathway was analyzed by reverse transcription-quan titative polymerase chain reaction (RT-qPCR) and Westernblot. Besides, PPAR-γ antagonist GW9662 and agonist rosiglitazone, AMPK antagonist compound C and activator AICAR as well as ACC inhibitor TOFA were used to further confirm the relationship between PPAR-γ and AMPK. RESULTS: The results demonstrated that Gentiopicroside markedly ameliorated hyperalgesia with prolonged paw withdrawal latency to heat and cold stimuli and fewer responses to mechanical allodynia compared with DPN model group. Gentiopicroside regulated dyslipidemia, enhanced nerve blood flow and improved MNCV as well as SNCV. Gentiopicroside suppressed ACC expression through the activation of AMPK and PPAR-γ mediated the activation of AMPK and subsequent inhibition of ACC expression. CONCLUSION: In conclusion, the present study demon strated that Gentiopicroside exerted nerve-protective effect and attenuated experimental DPN by restoring dyslipidmia and improved nerve blood flow through regulating PPAR-γ/AMPK/ACC signal pathway. These results provided a promising potential treatment of DPN.

Evaluation of density gradient ultracentrifugation serum lipoprotein profiles in healthy dogs and dogs with exocrine pancreatic insufficiency.

Changes in proportions of lipoprotein classes have been described in disease states in humans. In veterinary medicine, hyperlipidemia can cause complications, such as cutaneous xanthomas, liver disease, cholelithiasis, pancreatitis, glomerular disease, lipemia retinalis, or peripheral neuropathy, but there are few reports regarding lipoproteins in diseased animals. For canine serum, we partially validated continuous lipoprotein density profiling (CLPDP), a novel density gradient ultracentrifugation technique. We examined canine lipoproteins separated by CLPDP by transmission electron microscopy (TEM). We compared lipoprotein profiles between healthy control dogs ( n = 29) and dogs with exocrine pancreatic insufficiency (EPI; n = 28) using CLPDP. Dogs with EPI included those untreated (EPI-NT; n = 6) and those treated with enzyme supplementation (EPI-T; n = 22). Our preliminary assay validation showed that CLPDP was repeatable (CV = 11.2%) and reproducible (CV = 10.6%) in canine serum. The diameters of lipoproteins analyzed by TEM were similar to those reported previously. Dogs in the EPI-NT group had more severe dyslipidemia than dogs in the EPI-T group. Dogs in the EPI-T group had lipoprotein profiles similar to healthy control dogs. CLPDP might be a useful tool for evaluating dyslipidemia in dogs.

Spectrophotometry and Ultracentrifugation for Measurement of Plasma Lipids in Dogs with Diabetes Mellitus.

BACKGROUND: There are conflicting reports of plasma lipoprotein lipid content in dogs with diabetes mellitus (DM). OBJECTIVES: To determine lipoprotein lipid content of plasma of dogs with DM by spectrophotometry and ultracentrifugation; to compare lipoprotein lipid content in diabetic and healthy dogs; and to quantify apolipoprotein B-100 (ApoB) in dogs with DM. ANIMALS: 22 dogs with DM and 9 healthy dogs. METHODS: Cross-sectional study. Triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) concentrations were measured by spectrophotometry. Very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations were calculated after ultracentrifugation. Non-HDL-C cholesterol was calculated by subtracting HDL-C from TC. ApoB was quantified by ELISA. The Mann-Whitney test was used for comparison of median lipoprotein concentrations, and Spearman's correlation was used to assess associations between ApoB and lipoprotein fractions. RESULTS: All values are reported in mg/dL. Median TG (122), TC (343.5), HDL-C, (200), VLDL-C, (27) LDL-C (68), non-HDL-C (114), and ApoB (320) were significantly higher in dogs with DM, compared to healthy dogs (57, 197, 168, 12, 16, 31, and 258, respectively, P-values 0.0079, <0.001, 0.029, 0.011, <0.001, <0.001, 0.025, respectively). A significant association was found between ApoB and LDL-C (Spearman's rho = 0.41, P = 0.022) and between ApoB and non-HDL-C (Spearman's rho = 0.40, P = 0.027). CONCLUSIONS AND CLINICAL IMPORTANCE: Dyslipidemia of dogs with DM is characterized by pronounced increases in LDL-C and non-HDL-C concentrations, although all lipoprotein fractions are significantly increased. Knowledge of specific lipoprotein fraction alterations in dogs with DM can enhance treatment options for diabetic dyslipidemia in dogs.

Semi-synthetic thymoquinone analogs: new prototypes as potential antihyperlipidemics in irradiated rats.

AIM: Thymoquinone (TQ), has been reported to possess strong antihyperlipidemic properties. However, a variety of serious side effects has been reported for TQ. The present study aimed to evaluate the potential antihyperlipidemic activity of newly synthesized TQ analogs. METHODS & RESULTS: first, novel TQ derivatives were studied against radiation-induced dyslipidemia in male rats. Second, the most promising sulfur derivatives (4-7), were further tested to elucidate their possible mechanism(s) of actions. Results showed that they possess Hydroxymethyl Glutaryl-Co A reductase inhibitory activity, as well as stimulatory effects on the activities of each of plasma Lecithin-Cholesterol Acyltransferase and lipoprotein lipase enzymes. CONCLUSION: TQ derivatives (4-7), could be considered as promising agents in pathologies implicating impaired lipid metabolism, preclinical evaluation is warranted. [Formula: see text].

Análise do extrato aquoso de Arachis hipoagea L. no combate à dislipidemia e ao ganho ponderal de ratos Wistar submetidos à dieta hiperlipídica / Analysis of the aqueous extract of Arachis hipoagea L. to reduce dyslipidemia and weight gain in Wistar rats with high fat diet

O objetivo desse estudo foi avaliar os efeitos do Extrato Aquoso de Amendoim (EAA) no peso, bioquímica sérica e na histologia hepática de ratos Wistar submetidos a dietas normo e hiperlipídicas. A pesquisa foi realizada utilizando 40 ratos Wistar machos, divididos em quatro grupos (n=10): GA (dieta hiperlipídica), GB (dieta hiperlipídica +EAA), GC (dieta normolipídica) e GD (dieta normolipídica +EAA). Após 8 semanas, os animais foram eutanasiados e foram coletadas amostras sanguíneas para a avaliação de dados bioquímicos (Colesterol total e suas frações, triglicerídeos, uréia, creatinina, AST, ALT e glicemia) e fragmentos do fígado para análise histológica. Os animais do grupo GB tiveram um ganho de peso inferior quando comparados ao GA (XGB= versus XGA= p<0,05), já os grupos GC e GD não obtiveram diferenças estatísticas. Os animais que receberam o EAA tiveram uma redução nos níveis de colesterol (XGB= versus XGA= p<0,05 e XGD= versus XGA= p<0,01), dos triglicerídeos (XGB= versus XGA e XGD= versus XGA= p<0,001) e mais discretamente dos níveis de ALT. A glicemia, uréia e creatina permaneceram dentro dos valores de referência. As amostras hepáticas analisadas, dos ratos dos diferentes grupos, não apresentaram alterações histopatológicas. Conclui-se que O EAA apresentou efeitos preventivos sobre o ganho ponderal e dislipidemia.(AU)

The aim of this study was to evaluate the effect of Aqueous Extract from Peanut (EAA) in weight, serum biochemistry and liver histology of Wistar rats with normal hearing and a high fat diet. The survey was conducted using 40 male Wistar rats divided into four groups (n=0): GA (high fat diet), GB (fat diet+EAA), GC (normolipídica diet), and GD (normolipídica diet+EAA). After 8 weeks, the rats were euthanized and blood samples were collected to evaluate biochemical data (total cholesterol and its fractions, triglycerides, urea, creatinine, AST, ALT and glucose) and liver fragments for histological analysis. The animals of the GB group had a lower weight gain when compared with GA (XGB versus XGA= p<0.05), but CG and GD did not obtain statistical differences. The rats that received EAA had a reduction in cholesterol levels (XGB= versus XGA= p<0.05 vs. XGA and XGD= p<0.01), triglycerides (=XGB versus XGA and =XGD versus XGA= p<0,001) and more discreetly ALT levels. Blood glucose, urea and creatine remained within the reference values. Liver samples analyzed, the rats of different groups showed no histopathological changes. In conclusion, the EAA had preventive effects on weight gain and dyslipidemia.(AU)

Serum lipoprotein changes in dogs with renal disease.

BACKGROUND: People with renal disease develop a dyslipidemia that contributes to progression of renal injury and development of cardiovascular disease. Lipoproteins in dogs with renal disease have not been investigated. HYPOTHESIS: Dogs with chronic kidney disease (CKD) have dyslipidemia characterized by increased lower density lipoproteins and decreased high-density lipoproteins (HDLs). The degree of dyslipidemia is positively correlated with severity of disease, as reflected by serum creatinine concentration. ANIMALS: Prospective study of client-owned dogs presented to the Cornell University Hospital for Animals: 29 dogs with confirmed CKD, 5 dogs with nephrotic syndrome (NS), and 12 healthy control dogs presented for routine vaccinations, dental cleaning, or owned by students. METHODS: Lipoprotein electrophoresis was used to quantify relative proportions of the 3 main classes of lipoproteins in canine serum: low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), and HDL. Serum cholesterol and creatinine concentrations; urinalysis and urine protein-to-creatinine ratio were measured by standard methods. RESULTS: Dyslipidemia was consistently found in dogs with CKD and NS and was characterized by a decrease in HDL and variable increases in LDL and VLDL. Dogs with NS had a proportionately greater increase in the VLDL fraction, as compared with dogs with CKD. CONCLUSION AND CLINICAL IMPORTANCE: Dyslipidemia similar to that documented in people with renal disease occurs in dogs with CKD, despite serum cholesterol concentrations often being within the reference interval. The contribution of altered lipoproteins to the pathogenesis of renal disease in dogs warrants additional study.

Increases in beta-lipoproteins in hyperlipidemic and dyslipidemic dogs are associated with increased erythrocyte osmotic fragility.

BACKGROUND: The capacity of RBCs to traverse endothelium and deliver oxygen to tissues is dependent on a mechanically stable yet flexible plasma membrane. The lipid composition of the RBC membrane is crucial in maintaining its structure and fluidity. Lacking a nucleus and having minimal synthetic capacity, RBCs are exquisitely sensitive to changes in plasma lipids. OBJECTIVE: The objective of this study was to investigate the effects of plasma lipids on RBC fragility in hyperlipidemic and dyslipidemic dogs. METHODS: Osmotic fragility of RBCs, plasma lipoprotein fractions, and cholesterol and phospholipid content of RBC membranes were measured in hyperlipidemic, dyslipidemic, and healthy control dogs. Osmotic fragility of normal canine RBCs incubated in phosphate-buffered saline and in both intact and lipid-depleted plasma from diabetic dogs was also measured. RESULTS: RBCs from hyperlipidemic and dyslipidemic dogs with diabetes mellitus and dogs treated with glucocorticoids were significantly more fragile than RBCs from healthy control dogs. RBCs from hyperlipidemic dogs with cholestatic disease tended to be more stable relative to RBCs from controls. RBC osmotic fragility was positively correlated with beta-lipoprotein levels, but was only weakly correlated with serum cholesterol concentration. Incubation in plasma from hyperlipidemic diabetic dogs rendered RBCs from healthy dogs osmotically fragile, whereas lipid-depleted plasma from the same diabetic dogs had no effect. CONCLUSIONS: RBCs from hyperlipidemic and dyslipidemic dogs are osmotically fragile, and fragility is highly correlated with increases in beta-lipoproteins. Future studies are planned to address the consequences of lipid-induced fragility and subclinical hemolysis on endothelial cells, platelets, and coagulation.

Dyslipidemia in obese cats.

Obesity is an important endocrine disorder in cats and is a risk factor for diabetes similar to humans. The goal of this study was to examine the effect of long-term obesity and different diets (high protein, and high carbohydrate supplemented with saturated fatty acids or n-3 polyunsaturated fatty acids) on plasma lipids in the fasted and fed states in 12 lean (LEAN) and 12 obese (OBESE) cats with ultracentrifugation, and nuclear magnetic resonance spectroscopy. OBESE had higher plasma non-esterified fatty acids and triglycerides, as well as very-low-density-lipoproteins (VLDL) consisting primarily of medium-sized particles. The concentration of low-density-lipoproteins (LDL) was comparable between the groups, although OBESE had mostly very small, whereas LEAN had mostly large particles. The concentration of high-density-lipoproteins (HDL) was lower in OBESE and consisted primarily of small particles. Plasma triglycerides, and triglycerides and cholesterol in all lipoproteins increased postprandially. Different diets had little effect on lipids. Our results show that long-term obese cats develop similar lipoprotein changes to humans, yet, hypertension and atherosclerosis have not been described in obese cats. This suggests that dyslipidemia alone is not sufficient to induce hypertension and atherosclerosis. Other anti-atherogenic factors may be present in the obese, dyslipidemic cat.