Dietary Phospholipids Enhance Growth Performance and Modulate Cold Tolerance in Meagre (Argyrosomus regius) Juveniles

Meagre (Argyrosomus regius) is a fast-growing species currently produced in aquaculture. This species is highly sensitive to low environmental temperatures which results in high mortality events during production cycles. In this study, the effects of dietary phospholipids (PLs) on growth and cold tolerance were evaluated. For this purpose, control (CTRL) and PL-enriched diets (three-fold higher levels than CTRL) were supplied to meagre juveniles (12.9 ± 2.5g) for 60 days, and growth was determined using a longitudinal approach. Weight gaining and SGR reduction were significantly different between dietary treatments. Animals fed with the PL-enriched diet were 4.1% heavier and grew 3.2% faster than those fed with the CTRL diet. Survival was higher than 98% in both groups. After finishing the growth trial, animals were submitted to two cold challenges and cold tolerance was evaluated as temperature at death (Tdeath), risk to death and lethal doses (LD) 50 and 90 using the cumulative degree cooling hours 6 h (CD6H). Tdeath ranged between 7.54 and 7.91 °C without statistical differences between dietary treatments. However, risk to death was significantly smaller (0.91-fold lower) and LD50 and LD90 were higher in animals fed with the PL-enriched than those supplied the CTRL diet. To assess the fatty acid (FA) composition of liver and brain in animals fed both diets after a cold challenge, FA profiles were determined in juveniles maintained at 14 °C and challenged at 7 °C. FA amounts increased in the liver of animals challenged at 7 °C. In contrast, several FAs reduced their levels in the PL-enriched diet with respect to CTRL indicating that these animals were able to mobilize efficiently lipids from this organ mitigating the negative effects of lipid accumulation during the cold challenge. In brain, the PL-enriched diet increased DHA level during the cold shock indicating a role in maintaining of brain functions. These results open a new research line that could improve the cold tolerance of meagre through dietary supplementation before winter.

Cold-responsive adipocyte progenitors couple adrenergic signaling to immune cell activation to promote beige adipocyte accrual

The full array of cold-responsive cell types within white adipose tissue that drive thermogenic beige adipocyte biogenesis remains undefined. We demonstrate that acute cold challenge elicits striking transcriptomic changes specifically within DPP4+ PDGFRβ+ adipocyte precursor cells, including a β-adrenergic receptor CREB-mediated induction in the expression of the prothermogenic cytokine, Il33. Doxycycline-inducible deletion of Il33 in PDGFRβ+ cells at the onset of cold exposure attenuates ILC2 accumulation and beige adipocyte accrual. These studies highlight the multifaceted roles for adipocyte progenitors and the ability of select mesenchymal subpopulations to relay neuronal signals to tissue-resident immune cells in order to regulate tissue plasticity.

Metabolic physiology and skeletal muscle phenotypes in male and female myoglobin knockout mice

Myoglobin (Mb) is a regulator of O2 bioavailability in type I muscle and heart, at least when tissue O2 levels drop. Mb also plays a role in regulating cellular NO pools. Robust binding of long-chain fatty acids and long-chain acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout (KO) mice, suggests additional roles in muscle intermediary metabolism and fuel selection. To evaluate this hypothesis, we measured energy expenditure (EE), respiratory exchange ratio (RER), body weight gain and adiposity, glucose tolerance and insulin sensitivity in Mb knockout (Mb-/-) and wildtype (WT) mice challenged with a high fat diet (HFD, 45% of calories). In males (n=10/genotype) and females (n=9/genotype) aged 5-6, 11-12, and 17-18 wk, there were no genotype effects on RER, EE, or food intake. RER and EE during cold (10˚C, 72 h), and glucose and insulin tolerance, were not different compared to within-sex WT controls. At ~18 and ~19 wk of age, female Mb-/- adiposity was ~42-48% higher vs. WT females (p=0.1). Transcriptomics analyses (whole gastrocnemius, soleus) revealed few consistent changes, with the notable exception of a 20% drop in soleus transferrin receptor (Tfrc) mRNA. Capillarity indices were significantly increased in Mb-/-, specifically in Mb-rich soleus and deep gastrocnemius. The results indicate that Mb loss does not have a major impact on whole-body glucose homeostasis, EE, RER, or response to a cold challenge in mice. However, the greater adiposity in female Mb-/- mice indicates a sex-specific effect of Mb KO on fat storage and feed efficiency.

Convolutional Neural Networks for Differential Diagnosis of Raynaud’s Phenomenon Based on Hands Thermal Patterns

Raynaud’s phenomenon (RP) is a microvessels’ disorder resulting in transient ischemia. It can be either primary or secondary to connective tissue diseases, such as systemic sclerosis. The differentiation between primary and secondary to systemic sclerosis is of paramount importance to set the proper therapeutic strategy. Thus far, thermal infrared imaging has been employed to accomplish this task by monitoring the finger temperature response to a controlled cold challenge. A completely automated methodology based on deep convolutional neural network is here introduced with the purpose of being able to differentiate systemic sclerosis from primary RP patients by relying uniquely on thermal images of the hands acquired at rest. The classification performance of such a method was compared to that of a three-dimensional convolutional neural network model implemented to classify thermal images of the hands recorded during rewarming from a cold challenge. No significant differences were found between the two procedures, thus ensuring the possibility to avoid the cold challenge. Moreover, the convolutional neural network models were compared with standard feature-based approaches and showed higher performances, thus overcoming the limitations related to the feature extraction (e.g., biases introduced by the operator). Such automated procedures can constitute promising tools for large scale screening of primary RP and secondary to systemic sclerosis in clinical practice.

Thermoregulatory Responses and Performance of Dairy Calves Fed Different Amounts of Colostrum

This study investigates the newborn thermoregulatory responses to cold and the performance of calves fed different colostrum volumes. Thirty newborn Holstein calves were blocked by birth body weight (BW; 39.4 ± 6.5 kg) and fed different high-quality colostrum volumes: 10%, 15%, or 20% of BW, which was split and fed at 2 and 8 h after birth. At 24 h of life, calves were placed in a chamber at 10 °C for 150 min. Skin and rectal temperature (RT), heart and respiratory rate, and shivering were measured every 15 min. Blood samples were taken every 30 min. After the cold challenge, calves were housed in ambient temperature (26.8 ± 5.9 °C), with free access to water and concentrate and received 6 L/d of milk replacer. Feed intake, fecal score, and RT were recorded daily, until 56 d of age. Blood samples, BW, and body measures were taken weekly. During the cold challenge, prescapular temperature and total serum protein were greater for calves fed 15% or 20%. Leukocytes increased preweaning, presenting higher values for calves fed 20%. Even though there was a benefit for the calf submitted to cold stress on the first day of life, feeding higher volumes of colostrum resulted in no differences in performance during the preweaning phase. Nevertheless, calves fed a higher volume of colostrum (20% BW) presented increased immune responses during the preweaning phase.

Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus

Kdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a (LysM-Cre-Kdm2af/f, Kdm2a−/−) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a−/− increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a−/− mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following HFD challenge. Particularly, Kdm2a−/− macrophages provided a microenvironment in favor of thermogenesis. Upon HFD or cold challenge, the Kdm2a−/− mice manifested higher capacity for inducing adipose browning and beiging to promote energy expenditure. Collectively, our findings demonstrate the importance of Kdm2a-mediated H3K36 demethylation in orchestrating macrophage polarization, providing novel insight that targeting Kdm2a in macrophages could be a viable therapeutic approach against obesity and insulin resistance.

FGF2 disruption enhances thermogenesis in brown and beige fat to protect against obesity and hepatic steatosis

ABSTRACTSince brown and beige fat expend energy in the form of heat via non-shivering thermogenesis, identifying key regulators of thermogenic functions represents a major goal for development of potential therapeutic avenues for obesity and associated disorders. Here, we identified fibroblast growth factor 2 (FGF2) as a novel thermogenic regulator. FGF2 gene disruption resulted in increased thermogenic capability in both brown and beige fat, which was supported by increased UCP1 expression, enhanced respiratory exchange ratio, and elevated thermogenic potential under cold challenge or β-adrenergic stimulation. Thus, deletion of FGF2 protected mice from high fat-induced obesity and hepatic steatosis. Mechanistically, FGF2 acts in autocrine/paracrine fashions in vitro. Exogenous FGF2 supplementation inhibits both PGC-1α and PPARγ expression through ERK phosphorylation, thereby limiting PGC-1α/PPARγ interactions, and leading to suppression of UCP1 expression and thermogenic activity in brown and beige adipocytes. These findings suggest a viable potential strategy for use of FGF2-selective inhibitors in treatment of combating obesity and related disorders.

Finger blood flow after the cold challenge with primary Raynaud’s syndrome: a case report

Background Raynaud’s syndrome is a commonly encountered disorder. The relationship between the grade of Raynaud’s phenomenon and severity of vasoconstriction is unclear. Recently, various methods including colour Doppler ultrasonography have been used for assessment of vascularity of the extremities including fingers. Case summary A 53-year-old man had a 6-year history of Raynaud’s phenomenon with typical tri-coloured changes proceeding from white, blue to red and slight pain and slight paresthaesia in the fingers of both hands when his fingers were exposed to cold. He was diagnosed with primary Raynaud’s syndrome. After treatment with the calcium channel blocker amlodipine (5 mg once daily), a cold challenge did not induce Raynaud’s phenomenon on the fingers in the present patient. After the cold challenge, colour Doppler ultrasonography showed that vascularity was markedly decreased or was absent, whereas there was little difference in skin colour of the fingers. Discussion In Raynaud's phenomenon, vasospasm may occur even if the symptoms are well-controlled with a calcium channel blocker. It is unlikely that clinical symptoms in patients with Raynaud’s syndrome always reflect the severity of vasoconstriction in their fingers.