Lipid Mobilization Research Articles

The relationship between body condition score, thyroxin, and health condition and serum energy indices, insulin like growth factor-1, and lipids profile over the transition period in Holstein dairy cows.

Lipid mobilization increases significantly in cows around the time of calving; a correlation between excessive blood NEFA concentrations, oxidative stress, and impaired health status in transition dairy cattle was observed. The relationship between serum thyroxin (T4) values and energy indices and lipid profile in all cows, non-fat cows (NFCs), fat cows (FCs), healthy, and diseased animals were estimated in the present study. Blood samples were obtained from fifty multiparous cows on -14, +10, +20, and +30 days relative to parturition. They had similar diets and were kept under the same management conditions. NEFA and BHBA values increased significantly on the 10th day of calving. Inversely, glucose, T4, triglyceride, LDL-C, and VLDL-C decreased significantly ten days after calving. There was a significant negative correlation between serum T4 and NEFA for all cows and FCs. Serum T4 and BHBA values had a significant negative correlation in NFCs, FCs, healthy, and diseased cows. In addition, serum T4 and fructosamine had a significant negative relationship in FCs and a significant positive correlation in diseased cows. Serum T4 values had a significant negative correlation with cholesterol, HDL-C, and a positive correlation with triglyceride and VLDL-C for all cows, NFCs, FCs, and healthy cows. The data emphasized the effects of negative energy balance during the transition period on serum lipids profile and thyroid function. In addition, the correlation between T4 and energy and lipids indices may indicate a possible effect of health and body condition status on thyroid responses.

Interactions between polymyxin B and various bacterial membrane mimics: A molecular dynamics study

Polymyxin B (PMB) is clinically used as a last-line therapy against life-threatening Gram-negative “superbugs”. However, thorough understanding of the membrane actions of PMB at a molecular level is still lacking. In this work, a variety of bacterial membrane mimics with varying lipid compositions were built, and their interactions with PMB were systematically investigated using coarse-grained molecular dynamics simulation. PMB demonstrated characteristic preference to specific lipid species during its interaction with different membrane systems, such as the rough mutant lipipolysacchrides (Re LPS) preference in an outer membrane (OM) or the cardiolipin and POPG affinity in an inner membrane (IM). As a result of the lipid-specific actions, complicated membrane interaction states of PMB were observed, including adsorption on the OM surface. In contrast, for the IM or a mutative OM containing “impurity lipids” like POPE, POPG or lipid A, it could insert into the membrane via its acyl chain. Such actions of PMB influence the structure and lipid mobility of the membrane. In particular, the OM-bound PMB breaks the synchronous movement of Re LPS molecules in the outer leaflet and makes them diffuse more randomly, while its insertion into IM blocks the phospholipid diffusion and makes the membrane more homogeneous in the trajectory space. Our results provide insight into the action mechanism of PMB at a membrane level and a foundation for developing novel and safer polymyxin strategies for better clinical use.

NEFAs Influence the Inflammatory and Insulin Signaling Pathways Through TLR4 in Primary Calf Hepatocytes in vitro.

Transition dairy cows are often in a state of negative energy balance because of decreased dry matter intake and increased energy requirements, initiating lipid mobilization and leading to high serum β-hydroxybutyrate (BHBA) and non-esterified fatty acid (NEFAs) levels, which can induce ketosis and fatty liver in dairy cows. Inflammation and insulin resistance are also common diseases in the perinatal period of dairy cows. What is the relationship between negative energy balance, insulin resistance and inflammation in dairy cows? To study the role of non-esterified fatty acids in the nuclear factor kappa beta (NF-κB) inflammatory and insulin signaling pathways through Toll-like receptor 4 (TLR4), we cultured primary calf hepatocytes and added different concentrations of NEFAs to assess the mRNA and protein levels of inflammatory and insulin signaling pathways. Our experiments indicated that NEFAs could activate the NF-κB inflammatory signaling pathway and influence insulin resistance through TLR4. However, an inhibitor of TLR4 alleviated the inhibitory effects of NEFAs on the insulin pathway. In conclusion, all of these results indicate that high-dose NEFAs (2.4 mM) can activate the TLR4/NF-κB inflammatory signaling pathway and reduce the sensitivity of the insulin pathway through the TLR4/PI3K/AKT metabolic axis.

The presence of oxygenated lipids in plant defense in response to biotic stress: a metabolomics appraisal

ABSTRACT Recent lipid-based findings suggest more direct roles for fatty acids and their degradation products in inducing/modulating various aspects of plant defense, e.g. as signaling molecules following stress responses that may regulate plant innate immunity. The synthesis of oxylipins is a highly dynamic process and occurs in both a developmentally regulated mode and in response to abiotic and biotic stresses. This mini-review summarizes the occurrence of free – and oxygenated fatty acid derivatives in plants as part of an orchestrated metabolic defense against pathogen attack. Oxygenated C18 derived polyunsaturated fatty acids were identified by untargeted metabolomics studies of a number of different plant-microbe pathosystems and may serve as potential biomarkers of oxidative stress. Untargeted metabolomics in combination with targeted lipidomics, can uncover previously unrecognized aspects of lipid mobilization during plant defense.

Genome-wide identification and analysis of Oleosin gene family in four cotton species and its involvement in oil accumulation and germination

BackgroundCotton is not only a major textile fiber crop but also a vital oilseed, industrial, and forage crop. Oleosins are the structural proteins of oil bodies, influencing their size and the oil content in seeds. In addition, the degradation of oleosins is involved in the mobilization of lipid and oil bodies during seed germination. However, comprehensive identification and the systematic analysis of the Oleosin gene (OLEOs) family have not been conducted in cotton.ResultsAn in-depth analysis has enabled us to identify 25 and 24 OLEOs in tetraploid cotton species G. hirsutum and G. barbadense, respectively, while 12 and 13 OLEOs were identified in diploid species G. arboreum and G. raimondii, respectively. The 74 OLEOs were further clustered into three lineages according to the phylogenetic tree. Synteny analysis revealed that most of the OLEOs were conserved and that WGD or segmental duplications might drive their expansion. The transmembrane helices in GhOLEO proteins were predicted, and three transmembrane models were summarized, in which two were newly proposed. A total of 24 candidate miRNAs targeting GhOLEOs were predicted. Three highly expressed oil-related OLEOs, GH_A07G0501 (SL), GH_D10G0941 (SH), and GH_D01G1686 (U), were cloned, and their subcellular localization and function were analyzed. Their overexpression in Arabidopsis increased seed oil content and decreased seed germination rates.ConclusionWe identified OLEO gene family in four cotton species and performed comparative analyses of their relationships, conserved structure, synteny, and gene duplication. The subcellular localization and function of three highly expressed oil-related OLEOs were detected. These results lay the foundation for further functional characterization of OLEOs and improving seed oil content.

1H-NMR Plasma Lipoproteins Profile Analysis Reveals Lipid Metabolism Alterations in HER2-Positive Breast Cancer Patients.

Simple SummaryLipids’ metabolism deregulation is an established mark of breast cancer, however, no conclusive results have been reported on its effective role in disease development and progression. In this study, we applied straightforward 1H-NMR analysis to deeply explore alterations in circulating lipoproteins in HER2-positive breast cancer patients. The results support the key role played by lipids in the development of this breast cancer histotype and point out a specific lipid trait, characterized by a high plasma level of VLDL subfractions, potentially useful for diagnostic purposes. Moreover, the monitoring of plasma lipoproteins profile changes along the therapeutic interventions was found valuable to predict the clinical outcome.The lipid tumour demand may shape the host metabolism adapting the circulating lipids composition to its growth and progression needs. This study aims to exploit the straightforward 1H-NMR lipoproteins analysis to investigate the alterations of the circulating lipoproteins’ fractions in HER2-positive breast cancer and their modulations induced by treatments. The baseline 1H-NMR plasma lipoproteins profiles were measured in 43 HER2-positive breast cancer patients and compared with those of 28 healthy women. In a subset of 32 patients, longitudinal measurements were also performed along neoadjuvant chemotherapy, after surgery, adjuvant treatment, and during the two-year follow-up. Differences between groups were assessed by multivariate PLS-DA and by univariate analyses. The diagnostic power of lipoproteins subfractions was assessed by ROC curve, while lipoproteins time changes along interventions were investigated by ANOVA analysis. The PLS-DA model distinguished HER2-positive breast cancer patients from the control group with a sensitivity of 96.4% and specificity of 90.7%, mainly due to the differential levels of VLDLs subfractions that were significantly higher in the patients’ group. Neoadjuvant chemotherapy-induced a significant drop in the HDLs after the first three months of treatment and a specific decrease in the HDL-3 and HDL-4 subfractions were found significantly associated with the pathological complete response achievement. These results indicate that HER2-positive breast cancer is characterized by a significant host lipid mobilization that could be useful for diagnostic purposes. Moreover, the lipoproteins profiles alterations induced by the therapeutic interventions could predict the clinical outcome supporting the application of 1H-NMR lipoproteins profiles analysis for longitudinal monitoring of HER2-positive breast cancer in large clinical studies.

The autophagy protein ATG9A enables lipid mobilization from lipid droplets

The multispanning membrane protein ATG9A is a scramblase that flips phospholipids between the two membrane leaflets, thus contributing to the expansion of the phagophore membrane in the early stages of autophagy. Herein, we show that depletion of ATG9A does not only inhibit autophagy but also increases the size and/or number of lipid droplets in human cell lines and C. elegans. Moreover, ATG9A depletion blocks transfer of fatty acids from lipid droplets to mitochondria and, consequently, utilization of fatty acids in mitochondrial respiration. ATG9A localizes to vesicular-tubular clusters (VTCs) that are tightly associated with an ER subdomain enriched in another multispanning membrane scramblase, TMEM41B, and also in close proximity to phagophores, lipid droplets and mitochondria. These findings indicate that ATG9A plays a critical role in lipid mobilization from lipid droplets to autophagosomes and mitochondria, highlighting the importance of ATG9A in both autophagic and non-autophagic processes.

Ilex paraguariensisA. St.-Hil. (Yerba Mate) Differently Regulates the Lipid Mobilization and, Irisin and Lactate Levels in Sedentary and Chronic Swimming Mice

Healthy mice were submitted or not to daily chronic swimming and/or daily yerba mate (YM) infusion intake and had their bloods analyzed after four weeks. We hypothesized that daily intake of YM may act differently on lipid mobilization and, on the creatine, lactate and irisin levels in sedentary mice and those submitted to chronic exercise. The groups were (n=48): YM-non-treated control (NTC), YM-non-treated swimming control (NSC), non-roasted YM (NRY), roasted YM (RY), swimming plus non-roasted YM (SNRY), swimming plus roasted YM (SRY). No significant (P>0.05) difference was observed concerning creatine phosphoskinase (CPK) value. Lactate level decreased significantly (P<0.05) for SNRY and SRY, suggesting accelerated lipid mobilization and glycogen sparing potential. There was significant (P<0.05) body weight loss in all, except for NTC. Higher weight loss in NRY, RY, SNR and SRY indicated greater lipid mobilization. Thiobarbituric acid reactive substances (TBARS) and irisin had significantly (P<0.05) higher values for RY. This is first report that deals with the effect of YM consumption on serum irisin level. Major amounts of caffeic acid derivatives, slightly increased caffeine and less amount of rutin may be responsible by accelerated lipoperoxidation in sedentary healthy mices chronically treated with roasted YM. Chronically consumed YM plus swimming aid in healthy weight loss. Sedentary lifestyle plus roasted YM chronic consumption may cause accelerated lipid mobilization and increased TBARS production via irisin overexpression leading to an increase in lipoperoxidation.

Milk Odd and Branched Chain Fatty Acids in Dairy Cows: A Review on Dietary Factors and Its Consequences on Human Health.

Simple SummaryThe objective of this review is to highlight the importance of odd and branched chain fatty acids and dietary factors that may affect their content in milk acids in dairy cows. The primary source of odd and branched chain fatty acids is ruminal bacteria. In contrast to saturated fatty acids, odd and branched chain fatty acids have health protective effects against certain diseases as cardiovascular diseases, type II diabetes, cancers, Alzheimer’s disease and metabolic syndrome. Ruminant products are the main source of these fatty acids in the human diet. Odd and branched chain fatty acids profile in cow milk is mainly affected by dietary fatty acids and fatty acids metabolism in the rumen. Additionally, lipid mobilization in the body and fatty acids metabolism in mammary glands affect the milk odd and branched chain fatty acids profile. Understanding the origin of odd and branched chain fatty acids in milk and manipulating the diet of dairy cows to produce odd and branched chain fatty acids-enriched milk can be of scientific and industrial significance.This review highlights the importance of odd and branched chain fatty acids (OBCFAs) and dietary factors that may affect the content of milk OBCFAs in dairy cows. Historically, OBCFAs in cow milk had little significance due to their low concentrations compared to other milk fatty acids (FAs). The primary source of OBCFAs is ruminal bacteria. In general, FAs and OBCFAs profile in milk is mainly affected by dietary FAs and FAs metabolism in the rumen. Additionally, lipid mobilization in the body and FAs metabolism in mammary glands affect the milk OBCFAs profile. In cows, supplementation with fat rich in linoleic acid and α-linolenic acid decrease milk OBCFAs content, whereas supplementation with marine algae or fish oil increase milk OBCFAs content. Feeding more forage rather than concentrate increases the yield of some OBCFAs in milk. A high grass silage rate in the diet may increase milk total OBCFAs. In contrast to saturated FAs, OBCFAs have beneficial effects on cardiovascular diseases and type II diabetes. Furthermore, OBCFAs may have anti-cancer properties and prevent Alzheimer’s disease and metabolic syndrome.

Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy

BackgroundNon-alcoholic fatty liver disease (NAFLD) is characterized by ectopic accumulation of triglycerides in the liver. Emerging evidence has demonstrated that lipophagy regulates lipid mobilization and energy homeostasis in the liver. Sirtuin 3 (SIRT3), a mitochondrial NAD+-dependent deacetylase, modulates the activities of several substrates involving in autophagy and energy metabolism. Honokiol (HK) is a natural lignan from the plants of Magnolia genus that exhibits potent liver protective property.MethodsAML12 was challenged with 500 μM palmitic acid and 250 μM oleic acid mixture solution to induce lipotoxicity. C57BL/6J mice were fed with a choline-deficient high fat diet (CDHFD) to generate liver steatosis. The expression of autophagy-related and AMP-activated protein kinase (AMPK) pathway proteins was evaluated by Western blotting and immunofluorescence staining. Intracellular lipid accumulation was validated by Nile red staining. Molecular docking analysis was performed on AutoDock 4.2.ResultsHK (5 and 10 μM) was found to attenuate lipid accumulation through promoting SIRT3-AMPK-mediated autophagy, mainly on lipid droplets. HK had hydrophobic interaction with amino acid residues (PHE294, GLU323 and VAL324) and NAD+. Moreover, HK improved mitochondrial function to enhance lipolysis, through decreasing the acetylated long-chain acyl-CoA dehydrogenase level. In CDHFD-fed mice, HK (2.5 and 10 mg/Kg) treatment obviously prevented lipid accumulation in the liver. And co-treatment of the AMPK inhibitor, Compound C, almost abolished the above changes.ConclusionsThese results suggest that HK could ameliorate lipotoxicity in hepatocytes by activating SIRT3-AMPK-lipophagy axis, which might be a potential therapeutic agent against NAFLD.

Lipolysis: cellular mechanisms for lipid mobilization from fat stores.

The perception that intracellular lipolysis is a straightforward process that releases fatty acids from fat stores in adipose tissue to generate energy has experienced major revisions over the last two decades. The discovery of new lipolytic enzymes and coregulators, the demonstration that lipophagy and lysosomal lipolysis contribute to the degradation of cellular lipid stores and the characterization of numerous factors and signalling pathways that regulate lipid hydrolysis on transcriptional and post-transcriptional levels have revolutionized our understanding of lipolysis. In this review, we focus on the mechanisms that facilitate intracellular fatty-acid mobilization, drawing on canonical and noncanonical enzymatic pathways. We summarize how intracellular lipolysis affects lipid-mediated signalling, metabolic regulation and energy homeostasis in multiple organs. Finally, we examine how these processes affect pathogenesis and how lipolysis may be targeted to potentially prevent or treat various diseases.

Влияние голодания на мобилизацию жирных кислот из курдючного жира у баранчиков

In ruminants, adipose tissue performs 3 functions: synthesis of fatty acids, accumulation in the form of a reserve, and mobilization. After the esterification of fatty acids with the collected energy in adipocytes, triacyl-glycerols are born, and the esterification of fatty acids occurs by the α-glycerol-phosphate pathway. The volume of adipose tissue is determined not by the number of adiposites, but by their size. The metabolic activity of adiposites does not depend on the volume of fat collected in it or the volume of cytoplasm. This process in animals is regulated by energy balance. The purpose of the work was to study lipid metabolism and mobilization of fatty acids from tail fat during starvation in rams of the Karadolak and Bozag breeds. Materials and methods. A complex surgical operation was carried out according to the method of A. Aliyev on 9 heads of male rams of the Karabakh breed, the Karadolak line, the average live weight of which was 45.0±1.70 kg. Catheters were implanted in each ram in the carotid artery, in the portal vein of the liver, in the mesenteric vein and in the posterior vena cava (pointing towards the tail). Thus, from the difference in the concentration of metabolites in the arterial blood and in the blood of the portal vein, we obtained the data on the net absorption of metabolites from the gastrointestinal tract into the blood. And from the difference in lipid metabolites in arterial blood and in the blood of the posterior vena cava, we obtained data on their mobilization from tail fat. Results and discussion. The studies carried out have studied the effect of a fasting diet on the mobilization of fatty acids from tail fat. It became known that in rams of the Bozag and Karadolak breeds, during starvation, in order to meet the energy requirements of the body, there is a strong mobilization of total lipids and long-chain fatty acids. This process is most intensive in sheep of the Karadolak line, the Karabakh breed. In both breeds of sheep, during starvation, the amount of oleic acid in the lipids of the blood plasma taken from the posterior vena cava increased, and on the 5th day it reached its peak. This is due to the fact that the amount of oleic acid in the tail fat is higher compared to other fats. Therefore, after feeding, in both breeds of sheep, the amount of this acid decreased in plasma lipids, both arterial and venous (posterior vena cava) blood. After feeding A-B difference was positive. The percentage of linolenic and linoleic acids did not change during starvation in both breeds of sheep. Of the acids with carbon atom 20, dynamic changes have occurred in arachidonic acid. Since arachidonic acid is synthesized from linoleic acid, a close relationship of these acids in the blood is observed. During fasting, when linoleic acid is not supplied with food, the amount of arachidic acid in lipids decreased in blood plasma taken from the posterior vena cava. So, in sheep of the Karadolak breed, the amount of this acid decreased from 3.75 to 2.60, and in the Bozag breed from 5.24 to 2.33. Conclusion. In both breeds of sheep, in order to satisfy the body's need for energy, in connection with a starvation diet, there is a strong mobilization of total lipids and long-chain fatty acids from internal fat and tail fat. It should be noted that this process is clearly expressed in rams of the Karabakh breed of the Karadolak line

Glutamate metabolism directs energetic trade-offs to shape host-pathogen susceptibility in Drosophila

Individual hosts within populations often show inter-individual variation in their susceptibility to bacterial pathogen-related diseases. Utilizing Drosophila, we highlight that phenotypic variation in host-pathogen susceptibility within populations is driven by energetic trade-offs, facilitated by infection-mediated changes in glutamate metabolism. Furthermore, host-pathogen susceptibility is conditioned by life history, which adjusts immunometabolic sensing in muscles to direct vitamin-dependent reallocation of host energy substrates from the adipose tissue (i.e., a muscle-adipose tissue axis). Life history conditions inter-individual variation in the activation strength of intra-muscular NF-κB signaling. Limited intra-muscular NF-κB signaling activity allows for enhanced infection-mediated mitochondrial biogenesis and function, which stimulates glutamate dehydrogenase-dependent synthesis of glutamate. Muscle-derived glutamate acts as a systemic metabolite to promote lipid mobilization through modulating vitamin B enzymatic cofactor transport and function in the adipose tissue. This energy substrate reallocation improves pathogen clearance and boosts host survival. Finally, life history events that adjust energetic trade-offs can shape inter-individual variation in host-pathogen susceptibility after infection.

Loss of the ciliary gene Bbs4 results in defective thermogenesis due to metabolic inefficiency and impaired lipid metabolism.

Adipose tissue is central to the regulation of energy balance. While white adipose tissue (WAT) is responsible for triglyceride storage, brown adipose tissue specializes in energy expenditure. Deterioration of brown adipocyte function contributes to the development of metabolic complications like obesity and diabetes. These disorders are also leading symptoms of the Bardet-Biedl syndrome (BBS), a hereditary disorder in humans which is caused by dysfunctions of the primary cilium and which therefore belongs to the group of ciliopathies. The cilium is a hair-like organelle involved in cellular signal transduction. The BBSome, a supercomplex of several Bbs gene products, localizes to the basal body of cilia and is thought to be involved in protein sorting to and from the ciliary membrane. The effects of a functional BBSome on energy metabolism and lipid mobilization in brown and white adipocytes were tested in whole-body Bbs4 knockout mice that were subjected to metabolic challenges. Chronic cold exposure reveals cold-intolerance of knockout mice but also ameliorates the markers of metabolic pathology detected in knockouts prior to cold. Hepatic triglyceride content is markedly reduced in knockout mice while circulating lipids are elevated, altogether suggesting that defective lipid metabolism in adipose tissue creates increased demand for systemic lipid mobilization to meet energetic demands of reduced body temperatures. These findings taken together suggest that Bbs4 is essential for the regulation of adipose tissue lipid metabolism, representing a potential target to treat metabolic disorders.

Neuroimmune regulation of white adipose tissues.

The white adipose tissues (WAT) are located in distinct depots throughout the body. They serve as an energy reserve, providing fatty acids for other tissues via lipolysis when needed, and function as an endocrine organ to regulate systemic metabolism. Their activities are coordinated through intercellular communications among adipocytes and other cell types such as residential and infiltrating immune cells, which are collectively under neuronal control. The adipocytes and immune subtypes including macrophages/monocytes, eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2s), T and B cells, dendritic cells (DCs), and natural killer (NK) cells display cellular and functional diversity in response to the energy states and contribute to metabolic homeostasis and pathological conditions. Accumulating evidence reveals that neuronal innervations control lipid deposition and mobilization via regulating lipolysis, adipocyte size, and cellularity. Vice versa, the neuronal innervations and activity are influenced by cellular factors in the WAT. Though the literature describing adipose tissue cells is too extensive to cover in detail, we strive to highlight a selected list of neuronal and immune components in this review. The cell-to-cell communications and the perspective of neuroimmune regulation are emphasized to enlighten the potential therapeutic opportunities for treating metabolic disorders.

Perilipin 5 is a novel target of nuclear receptor LRH-1 to regulate hepatic triglycerides metabolism

Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism in maintaining a normal liver physiological state during fasting. The Lrh-1f/f and LRH-1 liver-specific knockout (Lrh-1LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. The livers were used for qPCR, western blot, and histological analysis. Primary hepatocytes were isolated for immunocytochemistry assessments of lipids. During fasting, the Lrh-1LKO mice showed increased accumulation of triglycerides in the liver compared to that in Lrh-1f/f mice. Interestingly, in the Lrh-1LKO liver, decreases in perilipin 5 (PLIN5) expression and genes involved in β-oxidation were observed. In addition, the LRH-1 agonist dialauroylphosphati-dylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed us to analyze the Plin5 promoter sequence, which revealed −1620/−1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immuno-precipitation assays. Additionally, fasted Lrh-1f/f primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted Lrh-1LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs, protect the liver from lipid overload, and manage the cellular needs during fasting.

Hepatic Injury Induced by Dietary Energy Level via Lipid Accumulation and Changed Metabolites in Growing Semi-Fine Wool Sheep.

Liver injury threatens the overall health of an organism, as it is the core organ of the animal body. Liver metabolism is affected by numerous factors, with dietary energy level being a crucial one. Therefore, the present study aimed to evaluate hepatic injury and to describe its metabolic mechanism in ruminants fed diets with different dietary energy levels. A total of 25 Yunnan semi-fine wool sheep were fed diets with five dietary metabolic energy levels and were randomly assigned to five groups as follows: low energy (LE), medium–low energy (MLE), medium energy (ME), medium–high energy (MHE), and high energy (HE). The results revealed that the average optical density (AOD) of lipid droplets in the LE, MLE, and HE groups was higher than that in the ME and MHE groups. The enzyme activity of alanine aminotransferase (ALT) was the lowest in the ME group. An increase in dietary energy level promoted the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity and altered the malondialdehyde (MDA) and protein carbonyl (PCO) concentration quadratically. In addition, both high and low dietary energy levels upregulated the mRNA abundance of proinflammatory cytokine interleukin (IL)-1β, nuclear factor-kappa B (NF-κB), and tumor necrosis factor (TNF)-α. Metabonomic analysis revealed that 142, 77, 65, and 108 differential metabolites were detected in the LE, MLE, MHE, and HE groups, compared with ME group respectively. These metabolites were involved in various biochemical pathways, such as glycolipid, bile acid, and lipid metabolism. In conclusion, both high and low dietary energy levels caused hepatic injury. Section staining and metabonomic results revealed that hepatic injury might be caused by altered metabolism and lipid accumulation induced by lipid mobilization.

Beyond the X Factor: Relevance of Sex Hormones in NAFLD Pathophysiology.

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, being frequently associated with obesity, unbalanced dietary regimens, and reduced physical activity. Despite their greater adiposity and reduced physical activity, women show a lower risk of developing NAFLD in comparison to men, likely a consequence of a sex-specific regulation of liver metabolism. In the liver, sex differences in the uptake, synthesis, oxidation, deposition, and mobilization of lipids, as well as in the regulation of inflammation, are associated with differences in NAFLD prevalence and progression between men and women. Given the major role of sex hormones in driving hepatic sexual dimorphism, this review will focus on the role of sex hormones and their signaling in the regulation of hepatic metabolism and in the molecular mechanisms triggering NAFLD development and progression.

Initial Liver Copper Status in Finishing Beef Steers Fed Three Dietary Concentrations of Copper Affects Beta Agonist Performance, Carcass Characteristics, Lipolysis Response, and Muscle Inflammation Markers.

Simple SummaryBeta agonists are commonly used in the United States beef industry, offering improved performance in the days leading up to harvest by influencing energy metabolism. Copper has been shown to regulate the biological pathway leading to increased lipid mobilization. However, this connection has not been evaluated in cattle. Therefore, the objective of this study was to determine how Cu influences beta agonist-induced performance, energy metabolism and inflammation in feedlot cattle. Supplementation of Cu resulted in increased liver Cu concentrations, while cattle performance, lipolysis, and some markers of inflammation responded to Cu supplementation differently, depending on whether or not cattle were fed a beta agonist. Therefore, strategic supplementation of Cu may help optimize growth of cattle receiving a beta agonist.Ninety-three Angus-crossbred steers (470 ± 35 kg) were assigned to a 3 × 2 factorial to determine the effects of Cu status and beta agonist (BA) on performance, carcass characteristics, lipolytic rate, and muscle inflammation. Factors included Cu supplementation (mg Cu/kg dry matter (DM)) at: 0 (LO), 10 (MED), or 20 (HI) from Cu amino acid complex (Availa Cu; Zinpro) with no BA (NoRAC) or 300 mg·steer−1·day−1 of ractopamine hydrochloride (RAC; Optaflexx; Elanco) for final 28 days of 88-day trial. Linear and quadratic effects of Cu status within BA treatment were tested. Pre-BA gain was not affected by Cu supplementation (p ≥ 0.57), although day 53 liver Cu quadratically increased (p = 0.01). Average daily gain and muscle IL-8 gene expression quadratically increased (p ≤ 0.01), with MED having greatest gain and gene expression. Ribeye area tended to quadratically increase with Cu supplementation within RAC (p = 0.08). In vitro basal lipolytic rate tended to quadratically increase with Cu supplementation within RAC (p = 0.11), while stimulated lipolytic rate tended to linearly increase within NoRAC (p = 0.10). These data suggest lipolysis and the BA response of steers are influenced by dietary and liver Cu concentrations.

Adipokinetic hormone (AKH), energy budget and their effect on feeding and gustatory processes of foraging honey bees

The adipokinetic hormone (AKH) of insects is considered an equivalent of the mammalian hormone glucagon as it induces fast mobilization of carbohydrates and lipids from the fat body upon starvation. Yet, in foraging honey bees, which lack fat body storage for carbohydrates, it was suggested that AKH may have lost its original function. Here we manipulated the energy budget of bee foragers to determine the effect of AKH on appetitive responses. As AKH participates in a cascade leading to acceptance of unpalatable substances in starved Drosophila, we also assessed its effect on foragers presented with sucrose solution spiked with salicin. Starved and partially-fed bees were topically exposed with different doses of AKH to determine if this hormone modifies food ingestion and sucrose responsiveness. We found a significant effect of the energy budget (i.e. starved vs. partially-fed) on the decision to ingest or respond to both pure sucrose solution and sucrose solution spiked with salicin, but no effect of AKH per se. These results are consistent with a loss of function of AKH in honey bee foragers, in accordance with a social life that implies storing energy resources in the hive, in amounts that exceed individual needs.