Diosgenin intervention: targeting lipophagy to counter high glucose diet-induced lipid accumulation and lifespan reduction.

Diosgenin (DG), a well-known steroidal sapogenin, is abundantly found in the plants of the Dioscoreaceae family and exhibits diverse pharmacological properties. In our previous study, we demonstrated that DG supplementation protected Caenorhabditis elegans from high glucose-induced lipid deposition, oxidative damage, and lifespan reduction. Nevertheless, the precise biological mechanisms underlying the beneficial effects of DG have not yet been described. In this context, the present study aims to elucidate how DG reduces molecular and cellular declines induced by high glucose, using the powerful genetics of the C. elegans model. Treatment with DG significantly (p < 0.01) prevented fat accumulation and extended lifespan under high-glucose conditions without affecting physiological functions. DG-induced lifespan extension was found to rely on longevity genes daf-2, daf-16, skn-1, glp-1, eat-2, let-363, and pha-4. Specifically, DG regulates lipophagy, the autophagy-mediated degradation of lipid droplets, in C. elegans, thereby inhibiting fat accumulation. Furthermore, DG treatment did not alter the triglyceride levels in the fat-6 and fat-7 single mutants and fat-6;fat-7 double mutants, indicating the significant role of stearoyl-CoA desaturase genes in mediating the reduction of fat deposition by DG. Our results provide new insight into the fat-reducing mechanisms of DG, which might develop into a multitarget drug for preventing obesity and associated health complications; however, preclinical studies are required to investigate the effect of DG on higher models. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04017-3.

Lactobacillus delbrueckii Ameliorated Blood Lipids via Intestinal Microbiota Modulation and Fecal Bile Acid Excretion in a Ningxiang Pig Model.

Lactobacillus delbrueckii intervention can regulate body lipid metabolism, but the underlying mechanism remains unclear. Our study investigated the effects of L. delbrueckii on serum lipid levels, tissular fat metabolism and deposition, bile acid metabolism, and gut microbiota in Ningxiang pigs. Ninety-six pigs were divided into two groups and fed basal diets containing either 0 (CON) or 0.1% L. delbrueckii (LD) for 60 days. Dietary L. delbrueckii promoted fecal total bile acid (TBA) excretion and increased hepatic enzyme activities related to cholesterol and bile synthesis but decreased hepatic and serum lipid concentrations. L. delbrueckii downregulated gene expression associated with fatty acid synthesis but upregulated gene expression related to lipolysis and ß-fatty acid oxidation in liver and subcutaneous fat. L. delbrueckii elevated gut Lactobacillus abundance and colonic short-chain fatty acid (SCFA)-producing bacteria but declined the abundance of some pathogenic bacteria. These findings demonstrated that L. delbrueckii modulated intestinal microbiota composition and facilitated fecal TBA excretion to regulate hepatic fat metabolism, which resulted in less lipid deposition in the liver and reduced levels of serum lipids.

Piceatannol Upregulates SIRT1 Expression in Skeletal Muscle Cells and in Human Whole Blood: In Vitro Assay and a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial.

Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, is reported to promote fat metabolism. This study investigated whether PIC affects sirtuin 1 (SIRT1) expression and metabolic factors in C2C12 skeletal muscle cells. C2C12 myotubes were stimulated with PIC, and alterations in gene expression, protein levels, mitochondrial DNA content, and fatty acid levels were assessed using real-time PCR, Western blotting, and Nile red staining. Furthermore, we examined changes in SIRT1 expression following the consumption of a test food containing 100 mg PIC for 2 weeks among adults with varying age and body mass index ranges. Both PIC and passion fruit seed extract induced SIRT1 expression in C2C12 myotubes to a greater extent than resveratrol. PIC also increased the expression of genes associated with mitochondrial biogenesis and fatty acid utilization, increased mitochondrial DNA content, and suppressed oleic acid-induced fat accumulation. Moreover, participants who consumed PIC exhibited significantly higher SIRT1 mRNA expression in whole blood compared to those in the placebo group. These findings suggest that PIC induces SIRT1 expression both in vitro and in the human body, which may promote mitochondrial biosynthesis and fat metabolism.

Interactions between PTH and adiposity: appetizing possibilities.

Although parathyroid hormone (PTH) is best known for its role as a regulator of skeletal remodelling and calcium homeostasis, more recent evidence supports a role for it in energy metabolism and other non-classical targets. In this report, we summarize evidence for an effect of PTH on adipocytes. This review is based upon all peer-reviewed papers, published in the English language with PubMed as the primary search engine. Recent preclinical studies have documented an effect of PTH to stimulate lipolysis in both adipocytes and liver cells and to cause browning of adipocytes. PTH also reduces bone marrow adiposity and hepatic steatosis. Although clinical studies are limited, disease models of PTH excess and PTH deficiency lend support to these preclinical findings. This review supports the concept of PTH as a polyfunctional hormone that influences energy metabolism as well as bone metabolism.

Parathyroid hormone controls skeletal and circulating calcium levels. Its secretion by the four parathyroid glands is regulated primarily by the concentration of the ionized calcium level. The other major target organ for parathyroid hormone is the kidney where it conserves filtered calcium by effects on the renal tubules. While bone and the kidney are indisputably the main target organs for PTH, recent studies are pointing to systems and organs that can be shown also to respond to PTH. One of these systems that PTH appears to target is fat cells, an important storehouse for energy. This review summarizes what is known about PTH's effects to stimulate the production of energy from fat cells when present in excess or to reduce the production of energy when deficient.

The cooperative regulatory effect of the miRNA-130 family on milk fat metabolism in dairy cows.

OBJECTIVE: There is a strong relationship between the content of beneficial fatty acids in milk and milk fat metabolic activity in the mammary gland. To improve milk quality, it is therefore necessary to study fatty acid metabolism in bovine mammary gland tissue. In adipose tissue, peroxisome proliferator-activated receptor gamma (PPARG), the core transcription factor, regulates the fatty acid metabolism gene network and determines fatty acid deposition. However, its regulatory effects on mammary gland fatty acid metabolism during lactation have rarely been reported. METHODS: Transcriptome sequencing was performed during the prelactation period and the peak lactation period to examine mRNA expression. The significant upregulation of PPARG drew our attention and led us to conduct further research. RESULTS: According to bioinformatics prediction, dual-luciferase reporter system detection, real-time quantitative reverse transcription polymerase chain reaction and Western blotting, miR-130a and miR-130b could directly target PPARG and inhibit its expression. Furthermore, triglyceride and oil red O staining proved that miR-130a and miR-130b inhibited milk fat metabolism in bovine mammary epithelial cells (BMECs), while PPARG promoted this metabolism. In addition, we also found that the coexpression of miR-130a and miR-130b significantly enhanced their ability to regulate milk fat metabolism. CONCLUSION: In conclusion, our findings indicated that miR-130a and miR-130b could target and repress PPARG and that they also have a functional superposition effect. miR-130a and miR-130b seem to synergistically regulate lipid catabolism via the control of PPARG in BMECs. In the long-term, these findings might be helpful in developing practical means to improve high-quality milk.

FAdV-4-induced ferroptosis affects fat metabolism in LMH cells.

Ferroptosis is a form of controlled cell death that was first described relatively recently and that is dependent on the formation and accumulation of lipid free radicals through an iron-mediated mechanism. A growing body of evidence supports the close relationship between pathogenic infections and ferroptotic cell death, particularly for viral infections. Ferroptosis is also closely tied to the pathogenic development of hepatic steatosis and other forms of liver disease. Fowl adenovirus serotype 4 (FAdV-4) is a hepatotropic aviadenovirus causing hydropericardium syndrome (HPS) that is capable of impacting fat metabolism. However, it remains uncertain as to what role, if any, ferroptotic death plays in the context of FAdV-4 infection. Here, FAdV-4 was found to promote ferroptosis via the p53-SLC7A11-GPX4 axis, while ferrostain-1 was capable of inhibiting this FAdV-4-mediated ferroptotic death through marked reductions in lipid peroxidation. The incidence of FAdV-4-induced fatty liver was also found to be associated with the activation of ferroptotic activity. Together, these results offer novel insights regarding potential approaches to treating HPS.

Progressive Arm Cycling Ergometry With 3- And 5-Minute Stage Durations Yields Similar Estimates of Substrate Oxidation in Healthy Adults.

Arm cycling ergometry (ACE) leads to a lower maximal oxygen uptake (VO2max) than cycling which is related to a smaller active muscle mass. This study compared estimates of fat and carbohydrate oxidation (FOx and CHOOx) between progressive exercise protocols varying in stage duration in an attempt to create a standard exercise protocol for determining substrate metabolism using ACE. Four men and seven women (age = 24 ± 9 yr) unfamiliar with ACE completed incremental exercise to determine peak power output and VO2peak. During two subsequent sessions completed after an overnight fast, they completed progressive ACE using 3- or 5-min stages during which FOx, CHOOx, and blood lactate concentration (BLa) were measured. Results showed no difference (p > 0.05) in FOx, CHOOx, or BLa across stage duration, and there was no difference in maximal fat oxidation (0.16 ± 0.08 vs. 0.13 ± 0.07 g/min, p = 0.07). However, respiratory exchange ratio in response to the 3 min stage duration was significantly lower than the 5 min duration (0.83 ± 0.05 vs. 0.86 ± 0.03, p = 0.04, Cohen's d = 0.76). Results suggest that a 3 min stage duration is preferred to assess substrate metabolism during upper-body exercise in healthy adults.

Fat malabsorption in critical illness.

Malnutrition in critical illness is common and is associated with significant increases in adverse outcomes. A hypermetabolic state and underfeeding both contribute to the incidence of malnutrition. Malabsorption caused by critical illness is also an important contributor to the development of malnutrition. The early provision of enteral nutrition is associated with improved outcomes. Strategies for nutrition therapy must be informed by the alterations in absorption of macronutrients present in these patients. The following review examines alterations in fat metabolism during critical illness, and its consequences to overall nutrition status. Critical illness, as well as the sequalae of common medical interventions, may lead to alterations in the mechanical and chemical processes by which fat is digested and absorbed. Mechanical alterations include delayed gastric emptying and changes to the normal gut transit time. Pharmacologic interventions aimed at reducing these impacts may themselves, negatively affect efficient fat absorption. Exocrine pancreatic insufficiency can also occur in critical illness and may be underappreciated as a cause of fat malabsorption. Dysfunction of the gut lymphatics has been proposed as a contributing factor to fat malabsorption, and additional work is needed to better describe and quantify those effects. Achieving optimal outcomes for nutrition therapy requires recognition of these alterations in fat digestion.

Smilax China L. polysaccharide prevents HFD induced-NAFLD by regulating hepatic fat metabolism and gut microbiota.

BACKGROUND: The increasing incidence of nonalcoholic fatty liver disease (NAFLD) has urged the development of new therapeutics. NAFLD is intimately linked to gut microbiota due to the hepatic portal system, and utilizing natural polysaccharides as prebiotics has become a prospective strategy for preventing NAFLD. Smilax china L. polysaccharide (SCP) possesses excellent hepatoprotective and anti-inflammatory activity. However, its protective effects on NAFLD remains unclear. PURPOSE: The goal of this study was to explore the protective effects of SCP on high-fat diet (HFD)-induced NAFLD mice by regulating hepatic fat metabolism and gut microbiota. METHODS: Extraction and isolation from Smilax china L. rhizome to obtain SCP. C57BL/6 J mice were distributed to six groups: Control (normal chow diet), HFD-fed mice were assigned to HFD, simvastatin (SVT), and low-, medium-, high-doses of SCP for 12 weeks. The body, liver, and different adipose tissues weights were detected, and lipids in serum and liver were assessed. RT-PCR and Western blot were used to detect the hepatic fat metabolism-related genes and proteins. Gut microbiota of cecum contents was profiled through 16S rRNA gene sequencing. RESULTS: SCP effectively reversed HFD-induced increase weights of body, liver, and different adipose tissues. Lipid levels of serum and liver were also significantly reduced after SCP intervention. According to the results of RT-PCR and western blot analysis, SCP treatment up-regulated the genes and proteins related to lipolysis were up-regulated, while lipogenesis-related genes and proteins were down-regulated. Furthermore, the HFD-induced dysbiosis of intestinal microbiota was similarly repaired by SCP intervention, including enriching beneficial bacteria and depleting harmful bacteria. CONCLUSION: SCP could effectively prevent HFD-induced NAFLD, might be considered as a prebiotic agent due to its excellent effects on altering hepatic fat metabolism and maintaining gut microbiota homeostasis.

Abnormal metabolism in hepatic stellate cells: Pandora's box of MAFLD related hepatocellular carcinoma.

Metabolic associated fatty liver disease (MAFLD) is a significant risk factor for the development of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), as key mediators in liver injury response, are believed to play a crucial role in the repair process of liver injury. However, in MAFLD patients, the normal metabolic and immunoregulatory mechanisms of HSCs become disrupted, leading to disturbances in the local microenvironment. Abnormally activated HSCs are heavily involved in the initiation and progression of HCC. The metabolic disorders and abnormal activation of HSCs not only initiate liver fibrosis but also contribute to carcinogenesis. In this review, we provide an overview of recent research progress on the relationship between the abnormal metabolism of HSCs and the local immune system in the liver, elucidating the mechanisms of immune imbalance caused by abnormally activated HSCs in MAFLD patients. Based on this understanding, we discuss the potential and challenges of metabolic-based and immunology-based mechanisms in the treatment of MAFLD-related HCC, with a specific focus on the role of HSCs in HCC progression and their potential as targets for anti-cancer therapy. This review aims to enhance researchers' understanding of the importance of HSCs in maintaining normal liver function and highlights the significance of HSCs in the progression of MAFLD-related HCC.

LncRNA ENSGALG00000021686 regulates fat metabolism in chicken hepatocytes via miR-146b/AGPAT2 pathway.

The liver contributes to lipid metabolism as the hub of fat synthesis. Long non-coding RNAs (lncRNAs) are considered the regulators of cellular processes. Since LncRNA ENSGALG00000021686 (lncRNA 21 686) has been described as a regulator of lipid metabolism, the present study aimed to clarify the role of lncRNA 21 686 in chicken hepatocytes' lipid metabolism. Thirty-two chickens were divided into four groups and were treated with diets containing different amounts of fat, and the hepatic expression of lncRNA 21 686 and miR-146b along with the levels of proteins involved in the regulation of fat metabolism, lipid indices and oxidative stress were measured. Moreover, primary chicken hepatocytes were transfected with lncRNA 21 686 small interfering RNA or microRNA (miRNA, miR)-146b mimics to measure the consequences of suppressing lncRNA or inducing miRNA expression on the levels of proteins involved in fat metabolism and stress markers. The results showed that the high-fat diet modulated the expression of lncRNA 21 686 and miR-146b (p-value < 0.001). Moreover, there was a significant increase in 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 (AGPAT2) gene expression and protein levels and modulated fat-related markers. Furthermore, the results showed that lncRNA 21 686 suppression reduced the expression of AGPAT2 and its downstream proteins (p-value < 0.05). Overexpression of miR-146b regulated fat metabolism indicator expression. Transfection experiments revealed that lncRNA 21 686 suppression increased miR-146b expression. The findings suggested a novel mechanism containing lncRNA 21 686/miR-146b/AGPAT2 in the regulation of fat metabolism in chicken hepatocytes.

Sulfur dioxide-free wine with polyphenols promotes lipid metabolism via the Nrf2 pathway and gut microbiota modulation.

Moderate wine consumption is often associated with preventing obesity, yet concerns arise due to the health risks linked to its constituent antioxidant, SO2. Recent focus has turned to polyphenols as a potential substitute for SO2. This investigation explores the impact and mechanisms of sulfur dioxide-free wine enriched with polyphenols on lipid regulation. Through a comprehensive analysis involving oxidative stress, lipid metabolism, and gut microorganisms in high-fat-diet mouse models, this study reveals that sulfur dioxide-free wine containing the polyphenol resveratrol exhibits a heightened ability to regulate lipids. It modulates oxidative stress by influencing NF-E2-related factor 2, a crucial factor, while enhancing lipid metabolism and fatty acid ß-oxidation through key genes such as carnitine palmitoyltransferase I and peroxisome proliferator-activated receptor alpha. Furthermore, oral administration of sulfur dioxide-free wine supplemented with resveratrol demonstrates an increase in the relative abundance of beneficial intestinal microflora, such as Turicibacter, Allobaculum, Bacteroides, and Macellibacteroides, while decreasing the Firmicutes/Bacteroidetes ratio.

The Potential Association of TFR1/SLC11A2/GPX4 with Ferroptosis in Mediating Lipid Metabolism Disorders in Atherosclerosis.

PURPOSE: Atherosclerosis is the most common and significant form of arterial disease, characterized primarily by lipid accumulation and inflammatory cell infiltration as its main pathological basis. This study aims to investigate the molecular mechanisms and associated pathways by which iron accumulation may be involved in lipid metabolism abnormalities in atherosclerotic mice. METHODS: Relying on ApoE-/- mouse body position observation, blood biochemical analysis, oxidative stress test and aortic tissue sectioning techniques, the effects of ferroptosis on lipid metabolism in atherosclerotic mice were analyzed. Use RT-PCR analysis and transcriptomics tests to understand the specific molecular mechanism. RESULTS: Our analysis reveals a correlation between Ferroptosis and elevated levels of TC, TG, ALT, AST, IL-1ß, and TNF-α in the blood of atherosclerotic model mice. At the same time, it exacerbates the pathological changes of mouse aorta tissue. Our results suggest a potential link between ferroptosis and the dysregulation of TFR1/SLC11A2/GPX4 expression, along with the presence of oxidative stress, in the progression of AS. Transcriptomics results indicate that ferroptosis- mediated deterioration of atherosclerosis in ApoE-/- mice is potentially associated with cell phagocytosis, apoptosis involving TNF-α, and the expression of atherosclerotic and other process-related genes. CONCLUSION: Ferroptosis exacerbated the lipid metabolism disorder in atherosclerotic mice. The core mechanism of its effect is that ferroptosis activates the TFR1/SLC11A2/GPX4 signaling pathway, which leads to the up-regulation of oxidative stress in ApoE-/- mice, and ultimately aggravates the abnormal lipid metabolism in ApoE-/- mice.

Effect of Acute Caffeine Intake on Fat Oxidation Rate during Fed-State Exercise: A Systematic Review and Meta-Analysis.

Pre-exercise intake of caffeine (from ~3 to 9 mg/kg) has been demonstrated as an effective supplementation strategy to increase fat oxidation during fasted exercise. However, a pre-exercise meal can alter the potential effect of caffeine on fat oxidation during exercise as caffeine modifies postprandial glycaemic and insulinemic responses. Hypothetically, the effect of caffeine on fat oxidation may be reduced or even withdrawn during fed-state exercise. The present systematic review aimed to meta-analyse investigations on the effect of acute caffeine intake on the rate of fat oxidation during submaximal aerobic exercise performed in the fed state (last meal < 5 h before exercise). A total of 18 crossover trials with randomised and placebo-controlled protocols and published between 1982 and 2021 were included, with a total of 228 participants (185 males and 43 females). Data were extracted to compare rates of fat oxidation during exercise with placebo and caffeine at the same exercise intensity, which reported 20 placebo-caffeine pairwise comparisons. A meta-analysis of the studies was performed, using the standardised mean difference (SMD) estimated from Hedges' g, with 95% confidence intervals (CI). In comparison with the placebo, caffeine increased the rate of fat oxidation during fed-state exercise (number of comparisons (n) = 20; p = 0.020, SMD = 0.65, 95% CI = 0.20 to 1.20). Only studies with a dose < 6 mg/kg of caffeine (n = 13) increased the rate of fat oxidation during fed-state exercise (p = 0.004, SMD = 0.86, 95% CI = 0.27 to 1.45), while no such effect was observed in studies with doses ≥6 mg/kg (n = 7; p = 0.97, SMD = -0.03, 95% CI = -1.40 to 1.35). The effect of caffeine on fat oxidation during fed-state exercise was observed in active untrained individuals (n = 13; p < 0.001, SMD = 0.84, 95% CI = 0.39 to 1.30) but not in aerobically trained participants (n = 7; p = 0.27, SMD = 0.50, 95% CI = -0.39 to 1.39). Likewise, the effect of caffeine on fat oxidation was observed in caffeine-naïve participants (n = 9; p < 0.001, SMD = 0.82, 95% CI = 0.45 to 1.19) but not in caffeine consumers (n = 3; p = 0.54, SMD = 0.57, 95% CI = -1.23 to 2.37). In conclusion, acute caffeine intake in combination with a meal ingested within 5 h before the onset of exercise increased the rate of fat oxidation during submaximal aerobic exercise. The magnitude of the effect of caffeine on fat oxidation during fed-state exercise may be modulated by the dose of caffeine administered (higher with <6 mg/kg than with ≥6 mg/kg), participants' aerobic fitness level (higher in active than in aerobically trained individuals), and habituation to caffeine (higher in caffeine-naïve than in caffeine consumers).

Screening of Genes Related to Fat Deposition of Pekin Ducks Based on Transcriptome Analysis.

Subcutaneous fat deposition is an important index with which to evaluate meat-producing ducks, and affects their meat quality and feed conversion rate. Studying the differentially expressed genes in subcutaneous fat will help to comprehensively understand the potential mechanisms regulating fat deposition in ducks. In this study, 72 Nankou 1 Pekin Ducks and 72 Jingdian Pekin Ducks (half male and half female) at 42 days of age were selected for slaughter performance and transcriptome analysis. The results showed that the breast-muscle yield of Nankou 1 ducks was significantly higher than that of Jingdian ducks, but that the abdominal fat yield and subcutaneous fat yield were higher than that of Jingdian ducks. Thousands of DEGs, including many important genes involved in fat metabolism regulation, were detected by transcriptome. KEGG enrichment analysis showed that the DEGs were significantly enriched on pathways such as regulation of lipolysis in adipocytes, primary bile acid biosynthesis, and biosynthesis of unsaturated fatty acids. SCD, FGF7, LTBP1, PNPLA3, ADCY2, and ACOT8 were selected as candidate genes for regulating subcutaneous fat deposition. The results indicated that Nankou 1 had superior fat deposition ability compared to Jingdian ducks, and that the candidate genes regulated fat deposition by regulating fat synthesis and decomposition.

Reproductive-dependent effects of B vitamin deficiency on lifespan and physiology.

B vitamins constitute essential micronutrients in animal organisms, executing crucial roles in numerous biological processes. B vitamin deficiency can result in severe health consequences, including the impairment of reproductive functions and increased susceptibility to age-related diseases. However, the understanding of how reproduction alters the requirements of each individual B vitamins for healthy aging and lifespan remains limited. Here, utilizing Drosophila as a model organism, we revealed the substantial impacts of deficiencies in specific B vitamins on lifespan and diverse physiological functions, with the effects being significantly shaped by reproductive status. Notably, the dietary absence of VB1, VB3, VB5, VB6, or VB7 significantly decreased the lifespan of wild-type females, yet demonstrated relatively little effect on ovoD1 infertile mutant females' lifespan. B vitamin deficiencies also resulted in distinct impacts on the reproduction, starvation tolerance and fat metabolism of wild-type females, though no apparent effects were observed in the infertile mutant females. Moreover, a deficiency in VB1 reshaped the impacts of macronutrient intervention on the physiology and lifespan of fertile females in a reproductive-dependent manner. Overall, our study unravels that the reproductive status of females serves as a critical modulator of the lifespan and physiological alterations elicited by B-vitamin deficiencies.

The prolactin receptor gene (PRLR) is linked and associated with the risk of polycystic ovarian syndrome.

The prolactin receptor gene (PRLR) may contribute to polycystic ovarian syndrome (PCOS) since it plays important roles in physiological ovarian functions. PRLR-knockout mice have irregular cycles and subfertility and variants in or around the PRLR gene were associated in humans with female testosterone levels and recurrent miscarriage. We tested 40 variants in the PRLR gene in 212 Italian families phenotyped by type 2 diabetes (T2D) and PCOS and found two intronic PRLR-variants (rs13436213 and rs1604428) significantly linked to and/or associated with the risk of PCOS. This is the first study to report PRLR as a novel risk gene in PCOS. Functional studies are needed to confirm these results.

Implications of TDP-43 in non-neuronal systems.

TAR DNA-binding protein 43 (TDP-43) is a versatile RNA/DNA-binding protein with multifaceted processes. While TDP-43 has been extensively studied in the context of degenerative diseases, recent evidence has also highlighted its crucial involvement in diverse life processes beyond neurodegeneration. Here, we mainly reviewed the function of TDP-43 in non-neurodegenerative physiological and pathological processes, including spermatogenesis, embryonic development, mammary gland development, tumor formation, and viral infection, highlighting its importance as a key regulatory factor for the maintenance of normal functions throughout life. TDP-43 exhibits diverse and sometimes opposite functionality across different cell types through various mechanisms, and its roles can shift at distinct stages within the same biological system. Consequently, TDP-43 operates in both a context-dependent and a stage-specific manner in response to a variety of internal and external stimuli. Video Abstract.

Supplementation of palmitoleic acid improved piglet growth and reduced body temperature drop upon cold exposure.

Piglet survival is a major challenge in the first few days postpartum and interventions during this period may improve survival and growth. This study investigated the effects of palmitoleic acid (C16:1n-7; PA) supplementation on growth performance, body temperature, fatty acid (FA), and energy metabolism in milk-replacer-fed piglets. Forty-eight piglets were stratified by body weight and randomly assigned to one of four dietary treatments (0%, 1%, 2%, and 3% PA supplementation as a percent of milk replacer) and given the diet through an orogastric tube. They were fed dietary treatments every 2 h for 4 d in the first week postpartum and all were sacrificed at the end of the experiment. The piglets were weighed daily, and half in each dietary treatment group, the same piglets each day, were exposed daily to a lower temperature for 2 h. Plasma samples were collected immediately before sacrifice for analyses of FA and other plasma metabolites. The weight of organs and empty body weight were determined after sacrifice. Liver and semimembranosus muscle tissue samples were collected and analyzed for FA content. Contents of C16:1n-7 and C18:1n-7 in both plasma and liver (P < 0.001), and C16:1n-7 in semimembranosus muscle (P < 0.001) increased linearly as PA supplementation increased. Most plasma FA levels (except C16:1n-7, C16:1n-9, and C22:5n-3) were lower in piglets exposed to lower temperatures than those that were not. Plasma glucose, triglycerides, and lactate dehydrogenase levels increased linearly with PA supplementation (P < 0.001). Piglets' average daily gain, liver glycogen pool, liver weight, and gallbladder weight increased linearly (P < 0.05, P < 0.01, P < 0.05, and P < 0.001, respectively), but lung weight, liver nitrogen content, and body temperature drop decreased linearly (P < 0.01, P < 0.001, and P < 0.05, respectively) with PA supplementation. Piglets exposed to low temperature had greater liver nitrogen (P < 0.05) and lactate dehydrogenase (P < 0.001) contents but had lower liver weight (P < 0.01) and plasma lactate concentration (P < 0.05) than those that were not. In conclusion, this study demonstrated the importance of PA on the growth performance of the piglets by increasing their average daily gain and decreasing a drop in body temperature upon cold exposure, most likely due to a modified energy metabolism.

Reducing piglet mortality in the early days after birth is a significant challenge in the modern pig industry. The focus on achieving larger litter sizes has had a negative impact on piglets' birth weight and their intake of colostrum. Additionally, piglets are born without easily oxidizable brown adipose tissue and have limited body reserves, making them more vulnerable to death due to their lower capacity for thermogenesis. Therefore, it is important to explore dietary strategies that can enhance piglets' thermogenesis capacity. In this study, the role of palmitoleic acid supplementation was investigated in a dose-response design to determine its impact on growth performance, fatty acid composition, and energy metabolism of milk-replacer-fed piglets during their first week of life. The results revealed a linear increase in the average daily gain of the piglets, liver weight, and liver glycogen content with increasing palmitoleic acid supplementation. Moreover, increased palmitoleic acid supplementation was associated with a drop in body temperature when piglets were exposed to a lower temperature during the experimental period. Altogether, the study indicated that palmitoleic acid has a sparing effect on glycogen reserves and that a greater proportion of energy utilized by the piglets to maintain their body temperature was derived from the oxidation of fatty acids. The results indicated a promising approach to improve piglet survival and growth through dietary modifications of fatty acids in the diet.

Cross-species analysis of differential transcript usage in humans and chickens with fatty liver disease.

Background and Aim: Fatty liver disease is a common condition, characterized by excess fat accumulation in the liver. It can contribute to more severe liver-related health issues, making it a critical concern in avian and human medicine. Apart from modifying the gene expression of liver cells, the disease also alters the expression of specific transcript isoforms, which might serve as new biological markers for both species. This study aimed to identify cross-species genes displaying differential expressions in their transcript isoforms in humans and chickens with fatty liver disease. Materials and Methods: We performed differential gene expression and differential transcript usage (DTU) analyses on messenger RNA datasets from the livers of both chickens and humans with fatty liver disease. Using appropriate cross-species gene identification methods, we reviewed the acquired candidate genes and their transcript isoforms to determine their potential role in fatty liver disease's pathogenesis. Results: We identified seven genes - ALG5, BRD7, DIABLO, RSU1, SFXN5, STIMATE, TJP3, and VDAC2 - and their corresponding transcript isoforms as potential candidates (false discovery rate ≤0.05). Our findings showed that these genes most likely contribute to fatty disease development and progression. Conclusion: This study successfully identified novel human-chicken DTU genes in fatty liver disease. Further research is encouraged to verify the functions and regulations of these transcript isoforms as potential diagnostic markers for fatty liver disease in humans and chickens.