Canine sterile steroid-responsive lymphadenitis in 49 dogs

OBJECTIVES:To report clinical and laboratory features, treatment responses and outcome in dogs diagnosed with sterile steroid-responsive lymphadenitis in the United Kingdom. MATERIALS AND METHODS:Medical records of dogs diagnosed with sterile steroid-responsive lymphadenitis from 2009 to 2016 at six specialist referral centres were evaluated retrospectively. RESULTS:The study included 49 dogs. Springer spaniels appeared to be over-represented (16 of 49 dogs). Young dogs (median age: 3 years and 9 months) and females (31 of 49) were frequently affected. Clinical presentation was variable, with pyrexia (39 of 49), lethargy (35 of 49) and anorexia (21 of 49) the most commonly reported clinical signs. Lymph node cytology or histopathology demonstrated neutrophilic, pyogranulomatous, granulomatous or necrotising lymphadenitis without a detectable underlying cause in all cases. Because a sterile immune-mediated aetiology was suspected, all dogs received prednisolone, which was followed by rapid resolution of clinical signs and lymphadenopathy in most cases. CLINICAL SIGNIFICANCE:Sterile steroid-responsive lymphadenitis should be considered in dogs with pyrexia of unknown origin with inflammatory lymphadenopathy if no underlying cause can be found and often responds well to immunosuppressive corticosteroid therapy

Nutrient supply affects the mRNA expression profile of the porcine skeletal muscle

Background: The genetic basis of muscle fat deposition in pigs is not well known. So far, we have only identified a limited number of genes involved in the absorption, transport, storage and catabolism of lipids. Such information is crucial to interpret, from a biological perspective, the results of genome-wide association analyses for intramuscular fat content and composition traits. Herewith, we have investigated how the ingestion of food changes gene expression in the gluteus medius muscle of Duroc pigs. Results: By comparing the muscle mRNA expression of fasted pigs (T0) with that of pigs sampled 5 h (T1) and 7 h (T2) after food intake, we have detected differential expression (DE) for 148 (T0-T1), 520 (T0-T2) and 135 (T1-T2) genes (q-value of 1.5). Many of these DE genes were transcription factors, suggesting that we have detected the coordinated response of the skeletal muscle to nutrient supply. We also found DE genes with a dual role in oxidative stress and angiogenesis (THBS1, THBS2 and TXNIP), two biological processes that are probably activated in the post-prandial state. Finally, we have identified several loci playing a key role in the modulation of circadian rhythms (ARNTL, PER1, PER2, BHLHE40, NR1D1, SIK1, CIART and CRY2), a result that indicates that the porcine muscle circadian clock is modulated by nutrition. Conclusion: We have shown that hundreds of genes change their expression in the porcine skeletal muscle in response to nutrient intake. Many of these loci do not have a known metabolic role, a result that suggests that our knowledge about the genetic basis of muscle energy homeostasis is still incomplete

Nutrients and the circadian clock: A partnership controlling adipose tissue function and health.

White adipose tissue (WAT) is a metabolic organ with flexibility to retract and expand based on energy storage and utilization needs, processes that are driven via the coordination of different cells within adipose tissue. WAT is comprised of mature adipocytes (MA) and cells of the stromal vascular cell fraction (SVF), which include adipose progenitor cells (APCs), adipose endothelial cells (AEC) and infiltrating immune cells. APCs have the ability to proliferate and undergo adipogenesis to form MA, the main constituents of WAT being predominantly composed of white, triglyceride-storing adipocytes with unilocular lipid droplets. While adiposity and adipose tissue health are controlled by diet and aging, the endogenous circadian (24-h) biological clock of the body is highly active in adipose tissue, from adipocyte progenitor cells to mature adipocytes, and may play a unique role in adipose tissue health and function. To some extent, 24-h rhythms in adipose tissue rely on rhythmic energy intake, but individual circadian clock proteins are also thought to be important for healthy fat. Here we discuss how and why the clock might be so important in this metabolic depot, and how temporal and qualitative aspects of energy intake play important roles in maintaining healthy fat throughout aging

Chronic supplementation of proanthocyanidins reduces postprandial lipemia and liver miR-33a and miR-122 levels in a dose-dependent manner in healthy rats

10.1016/j.jnutbio.2013.09.014Elevated postprandial triglycerides are associated with an increased risk of cardiovascular disease. Acute proanthocyanidin supplementation improves postprandial lipemia. Therefore, in this study, we evaluated whether a chronic treatment (3weeks) of grape seed proanthocyanidins (GSPE) improves tolerance to lipid overload and represses liver miRNA-33a and miRNA-122 and their target genes as a mechanism to soften the elevated postprandial triglycerides in healthy rats. Additionally, the minimal GSPE chronic dose required to alter miRNA levels was determined by means of a dose-response experiment using 5, 15, 25, or 50mg of GSPE/kg body weight. GSPE repressed miR-33a and miR-122 liver expression and reduced postprandial lipemia in a dose-dependent manner. Significant effects were only observed at high levels of proanthocyanidin consumption, but moderate doses of proanthocyanidins were still able to modulate miRNA expression. Therefore, it can be suggested that a population with a normal intake of proanthocyanidin-rich foods can benefit from the modulation of miRNA expression. At the molecular level, this action can confer homeostatic robustness and will thus exert subtle changes in lipid metabolism, thereby reducing the risk associated with postprandial hyperlipemia

Omega-3 polyunsaturated fatty acids and proanthocyanidins improve postprandial metabolic flexibility in rat

10.1002/biof.1129Postprandial lipemia influences the development of atherosclerosis, which itself constitutes a risk factor for the development of cardiovascular diseases. The introduction of bioactive compounds may prevent these deleterious effects. Proanthocyanidins are potent antioxidants that have hypolipidemic properties, while omega-3 polyunsaturated fatty acids (?3 PUFAs) stimulate fatty acid oxidation and gene expression programs, controlling mitochondrial functions. In this study, we investigated the effects of acute treatment of ?3 PUFAs and proanthocyanidins on the metabolic flexibility and lipid handling profiles in the skeletal muscle and adipose tissue of rats that were raised on diets, high in saturated fatty acids. For this, oil rich in docosahexaenoic (DHA-OR), grape seed proanthocyanidins extract (GSPE), or both substances (GSPE?+?DHA-OR) were administered with an overload of lard oil to healthy Wistar rats. Our results indicate that the addition of DHA-OR to lard oil increases insulin sensitivity and redirects fatty acids toward skeletal muscle, thereby activating fatty acid oxidation. We also observed an improvement in adipose mitochondrial functionality and uncoupling. In contrast, GSPE lowers lipidemia, prevents muscle reactive oxygen species (ROS) production and damage, furthermore, activates mitochondrial biogenesis and lipogenesis in adipose tissue. The addition of GSPE+DHA-OR to lard resulted in nearly all the effects of DHA-OR and GSPE administered individually, but the combined administration resulted in a more attenuated profile

Chronic Administration of Proanthocyanidins or Docosahexaenoic Acid Reversess the Increase of miR-33a and miR-122 in Dyslipidemic Obese Rats

10.1371/journal.pone.006981

Role of kallikrein 7 in body weight and fat mass regulation.

Increased plasma and adipose tissue protease activity is observed in patients with type 2 diabetes and obesity. It has been proposed that specific proteases contribute to the link between obesity, adipose tissue inflammation and metabolic diseases. We have recently shown that ablation of the serine protease kallikrein-related peptidase 7 (Klk7) specifically in adipose tissue preserves systemic insulin sensitivity and protects mice from obesity-related AT inflammation. Here, we investigated whether whole body Klk7 knockout (Klk7-/-) mice develop a phenotype distinct from that caused by reduced Klk7 expression in adipose tissue. Compared to littermate controls, Klk7-/- mice gain less body weight and fat mass both under chow and high fat diet (HFD) feeding, are hyper-responsive to exogenous insulin and exhibit preserved adipose tissue function due to adipocyte hyperplasia and lower inflammation. Klk7-/- mice exhibit increased adipose tissue thermogenesis, which is not related to altered thyroid function. These data strengthen our recently proposed role of Klk7 in the regulation of body weight, energy metabolism, and obesity-associated adipose tissue dysfunction. The protective effects of Klk7 deficiency in obesity are likely linked to a significant limitation of adipocyte hypertrophy. In conclusion, our data indicate potential application of specific KLK7 inhibitors to regulate KLK7 activity in the development of obesity and counteract obesity-associated inflammation and metabolic diseases

Publisher Correction: Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue.

The original version of this Article contained an error in Ref. 72, which was incorrectly given with the wrong author names as: Mendez-Ferrer, S., Lucas, D., Battista, M. & Frenette, P. S. Age-associated telomere attrition in adipocyte progenitors predisposes to metabolic disease. Nat. Metab. 2, 1482–1497 (2020). The correct form of Ref. 72 is: Gao, Z. et al. Age-associated telomere attrition in adipocyte progenitors predisposes to metabolic disease. Nat. Metab. 2, 1482–1497 (2020). This has been corrected in the PDF and HTML versions of the Article

Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue.

Hyperplastic expansion of white adipose tissue (WAT) relies in part on the proliferation of adipocyte precursor cells residing in the stromal vascular cell fraction (SVF) of WAT. This study reveals a circadian clock- and feeding-induced diurnal pattern of cell proliferation in the SVF of visceral and subcutaneous WAT in vivo, with higher proliferation of visceral adipocyte progenitor cells subsequent to feeding in lean mice. Fasting or loss of rhythmic feeding eliminates this diurnal proliferation, while high fat feeding or genetic disruption of the molecular circadian clock modifies the temporal expression of proliferation genes and impinges on diurnal SVF proliferation in eWAT. Surprisingly, high fat diet reversal, sufficient to reverse elevated SVF proliferation in eWAT, was insufficient in restoring diurnal patterns of SVF proliferation, suggesting that high fat diet induces a sustained disruption of the adipose circadian clock. In conclusion, the circadian clock and feeding simultaneously impart dynamic, regulatory control of adipocyte progenitor proliferation, which may be a critical determinant of adipose tissue expansion and health over time