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Cell Death & Disease Jun 2024Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in...
Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo Apoe and Apoo Ldlr mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.
Topics: Animals; Receptors, LDL; Cholesterol; NF-E2-Related Factor 2; Mice; Mice, Knockout; Mice, Inbred C57BL; Lipid Metabolism; Male; Atherosclerosis; Apolipoproteins; Humans; Liver; Apolipoproteins E; Hyperlipidemias
PubMed: 38830896
DOI: 10.1038/s41419-024-06778-4 -
Journal of Animal Science Jan 2024Angus-cross steers (n = 144; 362 kg ± 20.4) were used to determine the effect of Zn and steroidal implants on performance, trace mineral status, circulating...
Influence of steroidal implants and zinc sulfate supplementation on growth performance, trace mineral status, circulating metabolites, and transcriptional changes in skeletal muscle of feedlot steers.
Angus-cross steers (n = 144; 362 kg ± 20.4) were used to determine the effect of Zn and steroidal implants on performance, trace mineral status, circulating metabolites, and transcriptional changes occurring in skeletal muscle. Steers (n = 6 per pen) were stratified by body weight (BW) in a 3 × 2 factorial. GrowSafe bunks recorded individual feed intake (steer as experimental unit; n = 24 per treatment). Dietary treatments (ZINC; eight pens per treatment) included supplemental Zn as ZnSO4 at 1) 0 (analyzed 54 mg Zn/kg DM; Zn0); 2) 30 mg/kg DM (Zn30); 3) 100 mg Zn/kg DM (Zn100). After 60 d of Zn treatment, steers received a steroidal implant treatment (IMP) on day 0: 1) no implant; NO; or 2) high-potency combination implant (TE-200, Elanco, Greenfield, IN; 200 mg TBA, 20 mg E2; TE200). BWs were taken at days -60, 0, and in 28 d increments thereafter. Liver biopsies for TM analysis and blood for TM, serum glucose, insulin, nonesterified fatty acids (NEFA), urea-N, and IGF-1 analysis were collected on days 0, 20, 40, and 84. Glucose, NEFA, and insulin were used to calculate the revised quantitative insulin sensitivity check index (RQUICKI). Linear and quadratic effects of ZINC were evaluated in SAS 9.4. Means for IMP were separated using the LSMEANS statement with the PDIFF option. Day -60 BW was a covariate for performance and carcass data. Growth performance, plasma, liver, and metabolite data were analyzed as repeated measures. TE200 tended to decrease plasma Zn by 8.4% from days 0 to 20 while NO decreased by 3.6% (IMP × day; P = 0.08). A tendency for a ZINC × day effect on G:F was noted (P = 0.06) driven by Zn30 and Zn100 decreasing significantly from period 0-28 to period 28-56 while Zn0 was similar in both periods. An IMP × day effect was noted for RQUICKI where (P = 0.02) TE200 was greater on day 40 compared to NO cattle, but by day 84 RQUICKI was not different between TE200 and NO. On day 20, increasing Zn supplementation linearly increased mRNA abundance (P ≤ 0.09) of protein kinase B (AKT1), mammalian target of rapamycin (mTOR), matrix metalloproteinase 2 (MMP2), and myogenic factor 5 (MYF5). In this study, Zn and implants differentially affected genes related to energy metabolism, satellite cell function, and TM homeostasis on days 20 and 84 postimplant. These results suggest steroidal implants increase demand for Zn immediately following implant administration to support growth and may influence insulin sensitivity in finishing cattle.
Topics: Animals; Cattle; Male; Muscle, Skeletal; Dietary Supplements; Trace Elements; Zinc Sulfate; Drug Implants; Diet; Animal Feed; Trenbolone Acetate
PubMed: 38828800
DOI: 10.1093/jas/skae154 -
Cureus May 2024Perioperative neurocognitive disorders (PNDs) affect a large percentage of people who undergo surgeries that need general anesthesia. There is an increased risk of... (Review)
Review
Perioperative neurocognitive disorders (PNDs) affect a large percentage of people who undergo surgeries that need general anesthesia. There is an increased risk of death and a major disruption to postoperative self-care as a result of this. This study compiles all the relevant materials that the authors have found to investigate postnatal depression and its causes, as well as the methods used to determine the probability and severity of PNDs and how to reduce their risk before surgery. Postnatal depression can have many causes, and this text explores some of them. These include a history of alcohol or opiate use, immunological dysregulation, advanced age, educational background, infections, neurocognitive impairment, and pre-existing chronic inflammatory disorders. It also delves into various methods used to gauge the likelihood and severity of postpartum depression. The following assessment tools were covered: the Clock Drawing Test, Domain-Specific Tests, the Mini-Mental State Examination, and the Montreal Cognitive Assessment. In addition to biochemical markers, neuroimaging techniques play an important role in diagnosis. The Frailty Fried assessment, which measures inertia, sluggishness, lack of physical activity, fatigue, and unintentional weight loss, is a key prognostic sign that is highlighted. There is strong evidence that the index, which is derived from these five characteristics, may accurately predict the likelihood of PNDs. Risk mitigation strategies are also covered in this research. Preoperative brain plasticity-based therapies, such as physical exercise and intensive cognitive training, can significantly reduce the incidence and severity of postoperative neurocognitive disorders. A peripheral nerve block, monitoring cerebral oxygen saturation, dexmedetomidine, and a reduction in anesthesia depth are all ways to improve anesthetic procedures. Methods that lower blood pressure should be avoided, the body temperature should be kept down during surgery, or the time without liquids should be lengthened; all of these raise the risk of postoperative nausea and vomiting and make it worse. Potential approaches include a Mediterranean diet, physical activity, cognitive stimulation, smoking cessation, alcohol reduction, avoidance of anticholinergic medications, and non-steroidal anti-inflammatory drug stewardship, although there is no definitive evidence for successful postoperative neurocognitive rehabilitation procedures. More standardized diagnostic criteria, evaluation methods, and PND classification are urgently needed, according to this study. Different cases of PNDs are characterized by different combinations of tests, cutoff values, and methods because there is a broad variety of diagnostic tests used to make the diagnosis. Until now, PNDs and pre-existing neurocognitive disorders have been diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). With an aging population comes an increase in the occurrence and prevalence of PNDs, which calls for a specific way to classify and describe the condition.
PubMed: 38826940
DOI: 10.7759/cureus.59436 -
Case Reports in Hepatology 2024Drug-induced liver injury resulting from herbal and dietary supplement use is increasingly common and underrecognized. We report a case of a 34-year-old male...
Drug-induced liver injury resulting from herbal and dietary supplement use is increasingly common and underrecognized. We report a case of a 34-year-old male recreational bodybuilder who presented with muscle cramping, fatigue, and diffuse itching in the setting of bodybuilding supplement use. Labs showed cholestatic liver injury, and liver biopsy revealed bland cholestasis and sinusoidal dilation. He was diagnosed with anabolic-androgenic steroid-induced liver injury. He was symptomatically managed with plasmapheresis for debilitating pruritus. This case highlights drug-induced liver injury as a complication of bodybuilding supplement use containing unlabeled anabolic-androgenic steroids. Sports medicine providers should inquire on herbal and dietary supplement use and be aware of potential contaminants.
PubMed: 38826497
DOI: 10.1155/2024/5112461 -
Biological & Pharmaceutical Bulletin 2024Analysis of endogenous metabolites in various diseases is useful for searching diagnostic biomarkers and elucidating the molecular mechanisms of pathophysiology. The... (Review)
Review
Analysis of endogenous metabolites in various diseases is useful for searching diagnostic biomarkers and elucidating the molecular mechanisms of pathophysiology. The author and collaborators have developed some LC/tandem mass spectrometry (LC/MS/MS) methods for metabolites and applied them to disease-related samples. First, we identified urinary conjugated cholesterol metabolites and serum N-palmitoyl-O-phosphocholine serine as useful biomarkers for Niemann-Pick disease type C (NPC). For the purpose of intraoperative diagnosis of glioma patients, we developed the LC/MS/MS analysis methods for 2-hydroxyglutaric acid or cystine and found that they could be good differential biomarkers. For renal cell carcinoma, we searched for various biomarkers for early diagnosis, malignancy evaluation and recurrence prediction by global metabolome analysis and targeted LC/MS/MS analysis. In pathological analysis, we developed a simultaneous LC/MS/MS analysis method for 13 steroid hormones and applied it to NPC cells, we found 6 types of reductions in NPC model cells. For non-alcoholic steatohepatitis (NASH), model mice were prepared with special diet and plasma bile acids were measured, and as a result, hydrophilic bile acids were significantly increased. In addition, we developed an LC/MS/MS method for 17 sterols and analyzed liver cholesterol metabolites and found a decrease in phytosterols and cholesterol synthetic markers and an increase in non-enzymatic oxidative sterols in the pre-onset stage of NASH. We will continue to challenge themselves to add value to clinical practice based on cutting-edge analytical chemistry methodology.
Topics: Chromatography, Liquid; Animals; Humans; Biomarkers; Tandem Mass Spectrometry; Non-alcoholic Fatty Liver Disease; Carcinoma, Renal Cell; Niemann-Pick Disease, Type C; Glioma; Mice
PubMed: 38825462
DOI: 10.1248/bpb.b24-00073 -
Journal of Animal Science and... Jun 2024The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these...
BACKGROUND
The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows.
RESULTS
The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E (PGE) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE level. Importantly, PGE was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet.
CONCLUSIONS
Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet.
PubMed: 38822422
DOI: 10.1186/s40104-024-01034-3 -
Science Advances May 2024In response to energy and nutrient shortage, the liver triggers several catabolic processes to promote survival. Despite recent progress, the precise molecular...
In response to energy and nutrient shortage, the liver triggers several catabolic processes to promote survival. Despite recent progress, the precise molecular mechanisms regulating the hepatic adaptation to fasting remain incompletely characterized. Here, we report the identification of hydroxysteroid dehydrogenase-like 2 (HSDL2) as a mitochondrial protein highly induced by fasting. We show that the activation of PGC1α-PPARα and the inhibition of the PI3K-mTORC1 axis stimulate HSDL2 expression in hepatocytes. We found that HSDL2 depletion decreases cholesterol conversion to bile acids (BAs) and impairs FXR activity. HSDL2 knockdown also reduces mitochondrial respiration, fatty acid oxidation, and TCA cycle activity. Bioinformatics analyses revealed that hepatic expression positively associates with the postprandial excursion of various BA species in mice. We show that liver-specific HSDL2 depletion affects BA metabolism and decreases circulating cholesterol levels upon refeeding. Overall, our report identifies HSDL2 as a fasting-induced mitochondrial protein that links nutritional signals to BAs and cholesterol homeostasis.
Topics: Animals; Cholesterol; Bile Acids and Salts; Homeostasis; Mice; Fasting; Liver; Humans; Mitochondria; Signal Transduction; Hepatocytes; Male; Mechanistic Target of Rapamycin Complex 1
PubMed: 38820148
DOI: 10.1126/sciadv.adk9681 -
Scientific Reports May 2024Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully...
Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.
Topics: Animals; Female; Fibroblast Growth Factors; Mice, Transgenic; Mice; Linoleic Acids, Conjugated; Corticosterone; Dinoprostone; Glucagon; Epinephrine; Thermogenesis; Male; Lipid Metabolism; Adipose Tissue, Brown; Fatty Liver; Lipolysis; Hypertriglyceridemia; Adiposity
PubMed: 38816541
DOI: 10.1038/s41598-024-63282-7 -
Nutrition & Diabetes May 2024Vitamin D deficiency has been linked with several adverse maternal and fetal outcomes.
BACKGROUND
Vitamin D deficiency has been linked with several adverse maternal and fetal outcomes.
OBJECTIVE
To summarize systematic reviews and meta-analyses evaluating the effects of vitamin D deficiency and of vitamin D supplementation in pregnancy on maternal and offspring health-related outcomes.
METHODS
Prior to conducting this umbrella review, we registered the protocol in PROSPERO (CRD42022368003). We conducted searches in PubMed, Embase, and Cochrane Library for systematic reviews and meta-analyses on vitamin D in pregnancy, from database inception to October 2, 2023. All outcomes related to vitamin D in pregnancy obtained from the systematic reviews and meta-analyses were extracted.
DATA EXTRACTION
Two reviewers independently chose studies and collected information on health outcomes. The quality of the included articles' methodology was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews-2).
RESULTS
We identified 16 eligible systematic reviews and meta-analyses, which included 250,569 women. Our results demonstrated that vitamin D deficiency in pregnancy is associated with increased risk of preterm birth, small-for gestational age/low birth weight infants, recurrent miscarriage, bacterial vaginosis and gestational diabetes mellitus. Vitamin D supplementation in pregnancy increases birth weight, and reduces the risk of maternal pre-eclampsia, miscarriage, and vitamin D deficiency, fetal or neonatal mortality, as well as attention-deficit hyperactivity disorder, and autism spectrum disorder in childhood. In women with gestational diabetes mellitus, vitamin D supplementation in pregnancy can reduce the risk of maternal hyperbilirubinemia, polyhydramnios, macrosomia, fetal distress, and neonatal hospitalization.
CONCLUSION
Due to the association with adverse maternal and offspring health outcomes, we recommend the vitamin D status in pregnancy should be monitored, particularly in women at high risk of vitamin D deficiency. It is suggested that pregnant women take a dose of >400 IU/day of vitamin D supplementation during pregnancy to prevent certain adverse outcomes.
Topics: Humans; Pregnancy; Female; Vitamin D Deficiency; Vitamin D; Pregnancy Complications; Dietary Supplements; Pregnancy Outcome; Systematic Reviews as Topic; Meta-Analysis as Topic; Infant, Newborn; Premature Birth
PubMed: 38816412
DOI: 10.1038/s41387-024-00296-0 -
Turkish Journal of Medical Sciences 2023Multiple sclerosis (MS) may cause modifications in body composition, particularly for body fat associated with obesity and some biochemical parameters such as lipid...
BACKGROUND/AIM
Multiple sclerosis (MS) may cause modifications in body composition, particularly for body fat associated with obesity and some biochemical parameters such as lipid profiles. We investigated whether there is a link between the inflammatory contents of diets and body composition and lipid profiles in patients with MS.
MATERIALS AND METHODS
This was a cross-sectional study that included 85 MS patients. The study data of the patients were collected in the Neurology Clinic of Ondokuz Mayıs University's Health Practice and Research Center. The data included demographic characteristics; anthropometric measurements such as body weight, height, body mass index, waist circumference, hip circumference, body fat mass, body fat-free mass, and waist-hip ratio; and biochemical parameters such as high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol, triglyceride, and total cholesterol.
RESULTS
The body fat percentages of the patients were higher among those with proinflammatory diets (p < 0.05). Body fat percentage had a positive and very weak correlation with the Dietary Inflammatory Index (DII) score (rho = 0.206 and rho = 0.217, respectively; p < 0.05). HDL-c levels were higher in the group with high DII scores and there was a positive and weak correlation between HDL-c and DII scores (rho = 0.307, p < 0.05). Crude and adjusted linear regression models showed that the effect of HDL-c on DII scores was significant (p < 0.05).
CONCLUSION
We showed that DII scores, associated with the inflammatory potential of the diet and proinflammatory diets, may be associated with adiposity in MS patients and can be used from a clinical point of view for assessment.
Topics: Humans; Male; Female; Cross-Sectional Studies; Body Mass Index; Adult; Multiple Sclerosis; Adipose Tissue; Inflammation; Middle Aged; Lipids; Diet; Cholesterol, HDL; Body Composition
PubMed: 38813018
DOI: 10.55730/1300-0144.5681