Tissue Triglyceride Research Articles

Saturated Fats: Time to Assess Their Beneficial Role in a Healthful Diet

Saturated fats are widely seen as undesirable components of a healthy diet, as a result of their illusory association with elevated serum cholesterol. The regulation of serum cholesterol is now better understood and a lack of polyunsaturated fatty acids, rather than an abundance of saturated fatty acids, is responsible. Palmitic acid was shown to incite inflammation at unnaturally high concentrations in tissue culture, but later was found to play an auxiliary role as a precursor to ceramide biosynthesis and possibly in the palmitoylation of membrane receptors involved in the initiation of inflammation. Studies of arthritic inflammation in lab animals showed that dietary saturated fats are anti-inflammatory, whereas polyunsaturated oils are pro-inflammatory. Inflammation plays a role in numerous metabolic diseases, including insulin resistance, fatty liver disease and metabolic syndrome, among others. Fat, as triglycerides in adipose tissue, is an efficient way for living organisms to store energy and reduce the toxicity of other macronutrients. Macronutrients, such as excess carbohydrates and polyunsaturated fatty acids, are converted to saturated and monounsaturated fatty acids for storage as triglycerides in adipose tissue. Fatty acids are released from adipose tissue during fasting and as a result of some metabolic disorders, where elevated levels of nonesterified fatty acids in blood can lead to hepatic lipid accumulation, inflammation and insulin resistance. Although most serum nonesterified fatty acids may be saturated fatty acids, they are not necessarily derived from the diet. This paper will attempt to clarify the role of saturated fatty acids, and palmitic acid in particular, with regard to certain adverse health conditions.

Circadian Clock Disruption and Growth of Kidney Cysts in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 and PKD2 genes, and often progresses to kidney failure. ADPKD progression is not uniform among patients, suggesting that factors secondary to the PKD1/2 gene mutation could regulate the rate of disease progression. Here we tested the effect of circadian clock disruption on ADPKD progression. Circadian rhythms are regulated by cell-autonomous circadian clocks composed of clock proteins. BMAL1 is a core constituent of the circadian clock. To disrupt the circadian clock, we deleted Bmal1 gene in the renal collecting ducts of the Pkd1RC/RC (RC/RC) mouse model of ADPKD (RC/RC;Bmal1f/f;Pkhd1cre, called DKO mice), and in Pkd1 knockout mouse inner medullary collecting duct cells (Pkd1Bmal1KO mIMCD3 cells). Only male mice were used. Human nephrectomy ADPKD kidneys showed altered clock gene expression when compared to normal control human kidneys. When compared to RC/RC kidneys, DKO kidneys showed significantly altered clock gene expression, increased cyst growth, cell proliferation, apoptosis and fibrosis. DKO kidneys also showed increased lipogenesis and cholesterol synthesis-related gene expression, and increased tissue triglyceride levels compared to RC/RC kidneys. Similarly, in vitro, Pkd1Bmal1KO cells showed altered clock genes, increased lipogenesis and cholesterol synthesis-related genes, and reduced fatty-acid oxidation-related gene expression compared to Pkd1KO cells. The Pkd1Bmal1KO cells showed increased cell proliferation compared to Pkd1KO cells, which was rescued by pharmacological inhibition of lipogenesis. Renal collecting duct specific Bmal1 gene deletion disrupted the circadian clock and triggered accelerated ADPKD progression by altering lipid metabolism-related gene expression.

The Assessment of Anthropometric Measures and Changes in Selected Biochemical Parameters in Obese Children in Relation to Blood Lead Level.

Our paper draws attention to the impact of lead (Pb) on the specificity of obesity development in children exposed to environmental pollution. An advantage of this paper is the homogeneous study group comprising children of identical age from a single geographic region. Moreover, while the influence of environmental toxins on adults has been extensively explored, this study delves into pediatric populations, which have yet to receive comprehensive scrutiny within the scientific literature. Initially, a group of 136 obese children (the research program lasted three consecutive years: 2016, 2017, and 2018) living in the north-western region of Poland, from whom biochemical tests and auxological data were obtained, were enrolled for analysis. Blood lead levels (BLLs) were determined in 115 children. The age of the children ranged from 7.1 to 10.4 years. The body mass index (BMI) of children averaged 21.5 ± 2.2. The results showed that a large proportion of the participants had BLLs above the threshold for Pb. BLLs ≤ 5 µg/dL (considered safe for children and pregnant women) were found in over 70% of the participants, with BLLs in the range of 5.01-10.00 µg/dL in over 26% of the children, and concentrations > 10 µg/dL (considered toxic threshold for adults) in nearly 2% of the children. The results of our research revealed a positive association between BLLs and average systolic and diastolic blood pressure in the studied children. Moreover, we found a negative correlation between BLLs and absolute fat tissue content and triglyceride concentration. Among the included biochemical factors, only insulin demonstrated a statistically significant relationship with fat mass. This result suggests that early carbohydrate metabolism disorders in overweight children involve decreased peripheral tissue insulin sensitivity. Lead exposure may significantly contribute to the development of hypertension, insulin resistance, and glucose metabolism disorders in overweight and obese children. It is essential to implement multidirectional actions to increase awareness of the harmful effects of xenobiotic exposure, including lead, in order to prevent early-life exposure.

Modulation of SIRT6 related signaling pathways of p-AKT/mTOR and NRF2/HO-1 by memantine contributes to curbing the progression of tamoxifen/HFD-induced MASH in rats

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disorder marked by hepatic fat accumulation and inflammatory infiltrates which may evolve to cirrhosis. Clinical studies have demonstrated the higher risk of MASH development after tamoxifen (TAM) therapy, especially in obese patients. Therefore, we aimed to evaluate MASH induction by TAM combined with high fat diet (HFD) and the potential interference of memantine (MEMA) with MASH progression via modulation of SIRT6 and its related signaling pathways. MASH was induced in female Wistar rats by co-administration of TAM (25 mg/kg/day, p.o.) and HFD for 5 weeks. Liver function biomarkers, tissue triglyceride and cholesterol, MASH scoring, SIRT6 with its related signals, and lipid synthesis/oxidation markers were estimated. By comparison to MASH group, MEMA improved liver function indices (ALT, AST, ALP, albumin) and reduced the progression of MASH, evidenced by decreased accumulation of lipids in hepatic tissue, improved histological features, and reduced MASH scoring. MEMA enhanced hepatic SIRT6 and downregulated p-AKT/mTOR signaling, that subsequently reduced expressions of the lipid synthesis biomarkers (SREBP1c, SCD), while elevating the lipid oxidation markers (PPAR-α, CPT1). Moreover, MEMA enhanced NRF2/HO-1 signaling, with subsequently improved antioxidant defense and pro-inflammatory/anti-inflammatory cytokines balance. Analysis of SIRT6 correlations with p-AKT/mTOR, NRF2/HO-1, SREBP1c, and PPAR-α further confirmed our results. Consequently, we conclude that MEMA could interfere with MASH progression, at least in part, via enhanced SIRT6 expression and modulation of its related p-AKT/mTOR and NRF2/HO-1 signaling pathways, eventually reducing liver steatosis and inflammation. That could be a promising therapeutic modality for curbing MASH progression.

In-depth cerebrovascular lipidomics profiling for discovering novel biomarkers and mechanisms in moyamoya and intracranial atherosclerotic disease.

Despite considerable research efforts, the precise etiology and underlying pathways contributing to Moyamoya Disease (MMD) remain poorly understood. Moreover, the overlapping vascular pathologies shared between MMD and Intracranial Atherosclerotic Disease (ICAD) pose challenges in clinical differentiation, even with gold-standard cerebral angiography. An in-depth exploration of lipidomic alterations in cerebral intracranial MMD vessels could offer valuable insights into the pathogenesis of MMD-related mechanisms, encompassing MMD and ICAD, and unveil novel biomarkers and potential therapeutic targets. However, to date, comprehensive lipidomic profiling has been lacking. To discover novel biomarkers and unravel the pathophysiological mechanisms underlying MMD, we conducted a lipidomics analysis to characterize various lipid species in matched human extracranial and intracranial artery tissues from patients diagnosed with MMD (n=99) and ICAD (n=12). Our analysis identified 569 lipid species and delineated a robust panel of lipidomic biomarkers capable of effectively distinguishing MMD from ICAD (area under curve=0.98), as determined by receiver operating characteristic curve analysis. Notably, we observed a significantly more pronounced positive correlation of diacylglycerols and a negative association of triglycerides in intracranial artery tissues of MMD patients compared to those with ICAD, suggesting a potential role of dysregulated diacylglycerol-induced signaling in MMD pathogenesis. Furthermore, our investigation into the correlations of critical differential intracranial artery vessel lipid species between MMD and ICAD and clinical parameters revealed negative associations with plasma iron levels, implying a potential link between plasma iron metabolism and artery lipid homeostasis during MMD pathogenesis. These findings offer promising prospects for advancing clinical diagnosis for enhanced differentiation between the two disease conditions. Additionally, they shed light on the fundamental mechanisms implicated in MMD pathogenesis and suggest potential therapeutic avenues through targeting artery vessel lipids or plasma iron levels.

Doublecortin-like knockdown in mice attenuates obesity by stimulating energy expenditure in adipose tissue

Crosstalk between peripheral metabolic organs and the central nervous system is essential for body weight control. At the base of the hypothalamus, β-tanycytes surround the portal capillaries and function as gatekeepers to facilitate transfer of substances from the circulation into the cerebrospinal fluid and vice versa. Here, we investigated the role of the neuroplasticity gene doublecortin-like (DCL), highly expressed by β-tanycytes, in body weight control and whole-body energy metabolism. We demonstrated that DCL-knockdown through a doxycycline-inducible shRNA expression system prevents body weight gain by reducing adiposity in mice. DCL-knockdown slightly increased whole-body energy expenditure possibly as a result of elevated circulating thyroid hormones. In white adipose tissue (WAT) triglyceride uptake was increased while the average adipocyte cell size was reduced. At histological level we observed clear signs of browning, and thus increased thermogenesis in WAT. We found no indications for stimulated thermogenesis in brown adipose tissue (BAT). Altogether, we demonstrate an important, though subtle, role of tanycytic DCL in body weight control through regulation of energy expenditure, and specifically WAT browning. Elucidating mechanisms underlying the role of DCL in regulating brain-peripheral crosstalk further might identify new treatment targets for obesity.

Circadian clock disruption and growth of kidney cysts in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 and PKD2 genes, and often progresses to kidney failure. ADPKD progression is not uniform among patients, suggesting that factors secondary to the PKD1/2 gene mutation could regulate the rate of disease progression. Here we tested the effect of circadian clock disruption on ADPKD progression. Circadian rhythms are regulated by cell-autonomous circadian clocks composed of clock proteins. BMAL1 is a core constituent of the circadian clock. To disrupt the circadian clock, we deleted Bmal1 gene in the renal collecting ducts of the Pkd1 RC/RC (RC/RC) mouse model of ADPKD (RC/RC; Bmal1 f/f ; Pkhd1 cre , called DKO mice), and in Pkd1 knockout mouse inner medullary collecting duct cells ( Pkd1Bmal1 KO mIMCD3 cells). Only male mice were used. Human nephrectomy ADPKD kidneys and Pkd1 KO mIMCD3 cells showed reduced Bmal1 gene expression compared to normal controls. When compared to RC/RC kidneys, DKO kidneys showed significantly altered clock gene expression, increased cyst growth, cell proliferation, apoptosis and fibrosis. DKO kidneys also showed increased lipogenesis and cholesterol synthesis-related gene expression, and increased tissue triglyceride levels compared to RC/RC kidneys. Similarly, in vitro, Pkd1Bmal1 KO cells showed altered clock genes, increased lipogenesis and cholesterol synthesis-related genes, and reduced fatty-acid oxidation-related gene expression compared to Pkd1KO cells. The Pkd1Bmal1 KO cells showed increased cell proliferation compared to Pkd1KO cells, which was rescued by pharmacological inhibition of lipogenesis. Renal collecting duct specific Bmal1 gene deletion disrupts the circadian clock and triggers accelerated ADPKD progression by altering lipid metabolism-related gene expression. Lack of BMAL1, a circadian clock protein in renal collecting ducts disrupted the clock and increased cyst growth and fibrosis in an ADPKD mouse model.BMAL1 gene deletion increased cell proliferation by increasing lipogenesis in kidney cells.Thus, circadian clock disruption could be a risk factor for accelerated disease progression in patients with ADPKD.

Dietary bile acids supplementation decreases hepatic fat deposition with the involvement of altered gut microbiota and liver bile acids profile in broiler chickens

BackgroundHigh-fat diets (HFD) are known to enhance feed conversion ratio in broiler chickens, yet they can also result in hepatic fat accumulation. Bile acids (BAs) and gut microbiota also play key roles in the formation of fatty liver. In this study, our objective was to elucidate the mechanisms through which BA supplementation reduces hepatic fat deposition in broiler chickens, with a focus on the involvement of gut microbiota and liver BA composition.ResultsNewly hatched broiler chickens were allocated to either a low-fat diet (LFD) or HFD, supplemented with or without BAs, and subsequently assessed their impacts on gut microbiota, hepatic lipid metabolism, and hepatic BA composition. Our findings showed that BA supplementation significantly reduced plasma and liver tissue triglyceride (TG) levels in 42-day-old broiler chickens (P < 0.05), concurrently with a significant decrease in the expression levels of fatty acid synthase (FAS) in liver tissue (P < 0.05). These results suggest that BA supplementation effectively diminishes hepatic fat deposition. Under the LFD, BAs supplementation increased the BA content and ratio of Non 12-OH BAs/12-OH BAs in the liver and increased the Akkermansia abundance in cecum. Under the HFD, BA supplementation decreased the BAs and increased the relative abundances of chenodeoxycholic acid (CDCA) and cholic acid (CA) in hepatic tissue, while the relative abundances of Bacteroides were dramatically reduced and the Bifidobacterium, Escherichia, and Lactobacillus were increased in cecum. Correlation analyses showed a significant positive correlation between the Akkermansia abundance and Non 12-OH BA content under the LFD, and presented a significant negative correlation between the Bacteroides abundance and CA or CDCA content under the HFD.ConclusionsThe results indicate that supplementation of BAs in both LFD and HFD may ameliorate hepatic fat deposition in broiler chickens with the involvement of differentiated microbiota–bile acid profile pathways.Graphical

The effects of high-intensity interval training/moderate-intensity continuous training on the inhibition of fat accumulation in rats fed a high-fat diet during training and detraining

BackgroundCompared with moderate-intensity continuous training (MICT), high-intensity interval training (HIIT) has at least a comparable effect on inhibiting an increase in fat. However, few studies have been conducted to examine the effects of detraining on body fat in rats fed a high-fat diet. The present study aimed to compare the effects of 10 weeks of HIIT or MICT as well as 6 weeks of detraining on body fat in rats fed a high-fat diet.MethodsAfter being fed a high-fat diet for 8 weeks, 54 female rats were randomly assigned to six groups: (1) CON-10, sedentary control for 10 weeks; (2) MICT-10, 10 weeks of MICT; (3) HIIT-10, 10 weeks of HIIT; (4) CON-16, sedentary control for 16 weeks; (5) MICT-16, 10 weeks of MICT followed by 6 weeks of training cessation; and (6) HIIT-16, 10 weeks of HIIT followed by 6 weeks of training cessation. The training was performed 5 days/week. The subcutaneous adipose tissue (inguinal; SCAT), visceral adipose tissue (periuterine; VAT) and serum lipid profile were analysed after 10 or 16 weeks. Adipose tissue triglyceride lipase (ATGL) protein expression in VAT was assessed by western blotting.ResultsHIIT-10 and MICT-10 prevented the increase in SCAT, VAT and serum lipid levels seen in the CON group. During the 6-week detraining period, HIIT continued to prevent the increase in adipose tissue mass observed in the CON group, whereas MICT at least maintained this inhibition. The inhibition of fat mass increase was mainly the result of preventing adipocyte hypertrophy. The HIIT-10 and HIIT-16 groups showed the highest ATGL protein expression.ConclusionsHIIT has a comparable effect to MICT on inhibiting fat accumulation in female rats; however, the inhibition of SCAT and VAT increase by HIIT is superior to MICT after short-term training cessation.Graphical

Comparative analysis of energy homeostasis regulation at different altitudes in Hengduan Mountain of red-backed vole, Eothenomys miletus, during high-fat diet acclimation: examining gut microbial and physiological interactions.

The study aimed to explore the similarities and differences in gut microorganisms and their functions in regulating body mass in Eothenomys miletus across different altitudes in the Hengduan Mountains when exposed to a high-fat diet. Eothenomys miletus specimens were gathered from Dali (DL) and Xianggelila (XGLL) in Yunnan Province, China, and categorized into control, high-fat (1 week of high-fat diet), and re-feeding groups (1 week of high-fat diet followed by 2 weeks of standard food). The analysis utilized 16S rRNA sequencing to assess the diversity and structure of intestinal microbial communities in E. miletus. The investigation focused on the impact of high-fat diet consumption and different altitudes on gut microbial diversity, structure, and physiological markers. Results revealed that a high-fat diet influenced the beta diversity of gut microorganisms in E. miletus, leading to variations in microbial community structure between the two regions with different altitudes. High-fat food significantly affected body mass, white adipose tissue mass, triglycerides, and leptin levels, but not food intake. Specific intestinal microorganisms were observed in the high-fat groups, aiding in food digestion and being enriched in particular flora. In particular, microbial genera like Lactobacillus and Hylemonella were enriched in the high-fat group of DL. The enriched microbiota in the control group was associated with plant polysaccharide and cellulose decomposition. Following a high-fat diet, gut microbiota adapted to support lipid metabolism and energy supply, while upon re-feeding, the focus shifted back to cellulose digestion. These findings suggested that alterations in gut microbial composition, alongside physiological markers, play a vital role in adaptation of E. miletus to the diverse habitats of the Hengduan Mountains at varying altitudes.

Body Fat Distribution Contributes to Defining the Relationship between Insulin Resistance and Obesity in Human Diseases.

The risk for metabolic and cardiovascular complications of obesity is defined by body fat distribution rather than global adiposity. Unlike subcutaneous fat, visceral fat (including hepatic steatosis) reflects insulin resistance and predicts type 2 diabetes and cardiovascular disease. In humans, available evidence indicates that the ability to store triglycerides in the subcutaneous adipose tissue reflects enhanced insulin sensitivity. Prospective studies document an association between larger subcutaneous fat mass at baseline and reduced incidence of impaired glucose tolerance. Case-control studies reveal an association between genetic predisposition to insulin resistance and a lower amount of subcutaneous adipose tissue. Human peroxisome proliferator-activated receptorgamma (PPAR-γ) promotes subcutaneous adipocyte differentiation and subcutaneous fat deposition, improving insulin resistance and reducing visceral fat. Thiazolidinediones reproduce the effects of PPAR-γ activation and therefore increase the amount of subcutaneous fat while enhancing insulin sensitivity and reducing visceral fat. Partial or virtually complete lack of adipose tissue (lipodystrophy) is associated with insulin resistance and its clinical manifestations, including essential hypertension, hypertriglyceridemia, reduced HDL-c, type 2 diabetes, cardiovascular disease, and kidney disease. Patients with Prader Willi syndrome manifest severe subcutaneous obesity without insulin resistance. The impaired ability to accumulate fat in the subcutaneous adipose tissue may be due to deficient triglyceride synthesis, inadequate formation of lipid droplets, or defective adipocyte differentiation. Lean and obese humans develop insulin resistance when the capacity to store fat in the subcutaneous adipose tissue is exhausted and deposition of triglycerides is no longer attainable at that location. Existing adipocytes become large and reflect the presence of insulin resistance.

Conceivable Mechanisms of Clozapine Propagated Dyslipidemia- A Short Review

Abstract: Clozapine is the most effective drug for the treatment of refractory schizophrenia, showing a good response in the treatment of patients with resistant schizophrenia, especially in reducing violent, aggressive, and suicidal tendencies. However, treatment with clozapine has been associated with hyperlipidemia especially high triglycerides, obesity, diabetes, and cardiovascular disease. An elevated level of lipids has a direct impact on the improvement of symptoms in schizophrenics treated with clozapine. Although the mechanism is not clear, there is a possibility of serum lipids play a major part in enhancing clozapine's therapeutic activity. The effect of clozapine on phospholipids might indicate that this rise is related to its therapeutic benefit as well. Moreover, increased fatty acids accompanied by a sharp rise in triglycerides, point towards the possible involvement of lipases, which are involved in the storage and release of fatty acids and triglycerides in the adipose tissue. An increase in hepatic lipid synthesis can be another cause of hyperlipidemia and lead to weight gain over a certain period. Lipogenesis and myelin synthesis can also become targets in schizophrenia since myelination and synaptogenesis are essential in the central nervous system. Hence, the upregulation of several genes involved in cholesterol and fatty acid biosynthesis focused, which are proven to be controlled by Sterol regulating element-binding protein transcription factors (SREBP). The antipsychotic drug Clozapine activates this SREBP system. This activation increases lipogenesis which can be one of the mechanisms of action, which in turn could explain the metabolic side effects produced by clozapine.

Transgenic human C-reactive protein affects oxidative stress but not inflammation biomarkers in the aorta of spontaneously hypertensive rats

BackgroundC-reactive protein (CRP) is an acute inflammatory protein detected in obese patients with metabolic syndrome. Moreover, increased CRP levels have been linked with atherosclerotic disease, congestive heart failure, and ischemic heart disease, suggesting that it is not only a biomarker but also plays an active role in the pathophysiology of cardiovascular diseases. Since endothelial dysfunction plays an essential role in various cardiovascular pathologies and is characterized by increased expression of cell adhesion molecules and inflammatory markers, we aimed to detect specific markers of endothelial dysfunction, inflammation, and oxidative stress in spontaneously hypertensive rats (SHR) expressing human CRP. This model is genetically predisposed to the development of the metabolic syndrome.MethodsTransgenic SHR male rats (SHR-CRP) and non-transgenic SHR (SHR) at the age of 8 months were used. Metabolic profile (including serum and tissue triglyceride (TAG), serum insulin concentrations, insulin-stimulated incorporation of glucose, and serum non-esterified fatty acids (NEFA) levels) was measured. In addition, human serum CRP, MCP-1 (monocyte chemoattractant protein-1), and adiponectin were evaluated by means of ELISA, histological analysis was used to study morphological changes in the aorta, and western blot analysis of aortic tissue was performed to detect expression of endothelial, inflammatory, and oxidative stress markers.ResultsThe presence of human CRP was associated with significantly decreased insulin-stimulated glycogenesis in skeletal muscle, increased muscle and hepatic accumulation of TAG and decreased plasmatic cGMP concentrations, reduced adiponectin levels, and increased monocyte chemoattractant protein-1 (MCP-1) levels in the blood, suggesting pro-inflammatory and presence of multiple features of metabolic syndrome in SHR-CRP animals. Histological analysis of aortic sections did not reveal any visible morphological changes in animals from both SHR and SHR-CRP rats. Western blot analysis of the expression of proteins related to the proper function of endothelium demonstrated significant differences in the expression of p-eNOS/eNOS in the aorta, although endoglin (ENG) protein expression remained unaffected. In addition, the presence of human CRP in SHR in this study did not affect the expression of inflammatory markers, namely p-NFkB, P-selectin, and COX2 in the aorta. On the other hand, biomarkers related to oxidative stress, such as HO-1 and SOD3, were significantly changed, indicating the induction of oxidative stress.ConclusionsOur findings demonstrate that CRP alone cannot fully induce the expression of endothelial dysfunction biomarkers, suggesting other risk factors of cardiovascular disorders are necessary to be involved to induce endothelial dysfunction with CRP.

Nanoparticles loaded with the DNA methyltransferase inhibitor SGI-1027 decrease murine atherosclerosis and inflammation in cultured human macrophages

Aim: The DNA of the atheroma is hypermethylated relative to adjacent healthy vascular tissue. A significant portion of hypermethylated loci in the atheroma DNA map to genes related to macrophage function. Reversing macrophage DNA methylation to physiological levels by targeting DNA methyltransferase (DNMT) activity may therefore slow atherogenesis. Here, the anti-inflammatory and anti-atherogenic activity of macrophage-targeted DNMT inhibitor SGI-1027 were tested. Methods: SGI-1027 was encapsulated into human serum albumin (HSA) nanoparticle (HSANP) functionalized with the PP1 peptide, a macrophage scavenger receptor 1 ligand, fused to a FLAG epitope (S-HSANP-FLAGPP1). Results: Nanoparticle physico-chemical characteristics predicted good marginalization towards the vascular wall, although SGI-1027 encapsulation efficiency was relatively low (~23%). S-HSANP-FLAGPP1 were rapidly internalized compared to non-functionalized and, surprisingly, functionalized void controls, and induced a shift towards an anti-inflammatory profile of secreted cytokines in human THP-1 macrophages. S-HSANP-FLAGPP1 colonized the atheroma and induced a significant ~44% reduction of atherosclerosis burden in the aortic tree of apolipoprotein E (ApoE)-null mice compared to controls. A reduction in aortic root atherosclerosis was observed, although primarily induced by HSANP irrespective of loading or functionalization. No alteration of body weight, non-vascular tissue gross histology, plasma glucose, triglyceride or cholesterol were observed. HSA whether free or structured in nanoparticles, induced a 3–4-fold increase in high-density lipoprotein (HDL) compared to vehicle. Conclusions: Unexpectedly, effects that were likely non-epigenetic and induced by HSA per se were observed. HSANP loaded with SGI-1027 were anti-atherogenic but in an anatomical location-dependent fashion. SGI-1027 displayed a novel anti-inflammatory activity in non-proliferating THP-1 cells, implying that those effects are likely unrelated to DNMT inhibition. HSA elevated HDL per se, thus underlining a possible additional advantage of HSA-based nanocarriers.

Salvia officinalis Improves Glycemia and Suppresses Pro-inflammatory Features in Obese Rats with Metabolic Syndrome.

Obesity is regarded as the main cause of metabolic diseases and a core factor for all-cause mortality in the general population, notably from cardiovascular disease. The majority of people with type 2 diabetes have obesity and insulin resistance. Some evidence indicates that an individual with obesity is approximately 10 times more likely to develop type 2 diabetes than someone with moderate body weight. One of the most significant therapeutic herbs, Salvia officinalis (Lamiaceae) (SAGE), possesses potent medicinal importance. The aim of this article was to evaluate the anti-diabetic and antiobesity activity of SAGEAE against HFD-induced obesity in rats. Thirty adult albino rats were randomly divided into five equal groups: control, High-fat Diet (HFD) administrated rats, HFD + Salvia officinalis Aqueous Extract (SAGEAE) (150 mg/kg.bw.), HFD + SAGEAE (300 mg/kg.bw.) and HFD + metformin (500 mg/kg.bw.). Body weight, plasma biochemical parameters, oxidative stress, inflammatory indicators, hepatic Phosphoenolpyruvate Carboxykinase 1 (PCK1), Glucokinase (GK), brain Leptin Receptor (LepRb), Glucose Transporter-4 (GLUT4), Sirtuin 1 (SIRT1) and mRNA33-5P gene signalling mRNA levels were all assessed after 8 weeks. A histological examination of the liver was also performed to check for lipid accumulation. The administration of HFD resulted in increased body weight, glucose, insulin, leptin, Total Cholesterol (TC), Triglycerides (TG), Thiobarbaturic Acid Reactive Substances (TBARS), Monocyte Chemoattractant Protein-1 (MCP1), Interleukine-6 (IL-6) and tumor necrosis factor-α (TNF- α) as well as hepatic PCK1, brain LepRb and adipose tissue mRNA33-5P gene expression. However, our findings revealed a significant reduction in adiponectin, High-density Lipoproteincholesterol (HDL-C), reduced glutathione (GSH) and Superoxide Dismutase (SOD) levels as well as the expression of hepatic GK and adipose tissue SIRT1 and GLUT4 genes. Also, administration of SAGEAE significantly normalized body weight, glucose, insulin, leptin, adiponectin, TC, TG, HDL-C, TBARs, SOD, IL-6, MCP-1 and TNF-α in plasma and liver tissue of HFD-treated rats. On the other hand, PCK1, GK, LepRb, SIRT1, GLUT4 and mRNA33-5P gene expression was enhanced in obese rats when administrated with SAGEAE. Histological and US studies support the biochemical, PCR and electrophoretic results. The findings imply that SAGEAE could be used as a new pharmaceutical formula in the treatment of obesity.

Trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) purified from freshwater clams markedly alleviates dimethylnitrosamine-induced hepatic fibrosis.

Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression of fibrosis-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-β), as well as the hydroxyproline content, which decreased after treatment with FCE and TNHD. Animal experiments revealed that FCE and TNHD can reduce liver fibrosis by inhibiting cytokines that activate stellate cells and decreasing extracellular matrix (ECM) secretion. Cell experiments have shown that TNHD inhibits the MAPK/Smad signaling pathway and TGF-β1 activation, resulting in a reduction in the expression of fibrosis-related proteins. Therefore, freshwater clam extracts, particularly TNHD, may have potential therapeutic and preventive effects for the amelioration of liver fibrosis.

Extract mixture of plants (OXYLIA) inhibits fat accumulation by blocking FAS-related factors and promoting lipolysis via cAMP-dependent PKA activation.

Obesity is characterized by an imbalance between energy intake and expenditure, leading to the excessive accumulation of triglycerides in adipose tissue. This study investigated the potential of Oxylia to prevent obesity in mice fed with a high-fat diet (HFD). C57BL/6J mice were fed with one of the following five diets - AIN93G normal diet (normal control), 60% (HFD; control), HFD containing metformin at 40 mg/kg body weight (b.w.) (Met; positive control), HFD containing Oxylia at 30 mg/kg b.w. (O30), or HFD containing Oxylia at 60 mg/kg b.w. (O60) - for 15 weeks. Mice under an HFD supplemented with Oxylia had decreased body weight gain, adipose tissue weight, and adipose tissue mass. In addition, triglyceride (TG), total cholesterol, and VLDL/LDL cholesterol levels were lower in the O60 groups than in the HFD-fed control group. Moreover, Oxylia supplementation decreased the expression of adipogenesis-related mRNAs and lipogenesis-related proteins while increasing the expression of lipolysis-related proteins in white adipose tissue and thermogenesis-related proteins in brown adipose tissue. These findings suggest that Oxylia has potential as a functional food ingredient for the prevention and treatment of obesity and related metabolic disorders.

The Effectiveness of Low-Carb Diet vs Low-Fat Diet on Body Composition in People with Obesity: A Literature Review

Background: Obesity is still become a serious problem today. Obesity is caused by excessive adipose tissue. One of many factors that contribute to a person's obesity is food intake. Excess carbohydrate and fat intake will be stored in the form of triglycerides in adipose tissue. In the meantime, Low-Carb Diet (LCD) and Low-Fat Diet (LFD) are one of the most popular treatments on obesity. However there are many pros and cons related to each diet based on several studies. Objectives: The indicated study aims to determine the effectiveness of LCD and LFD on body composition in people with obesity. Methods: The study was conducted through journal and literature review, based on five journal publications, filtered by related keywords. In accordance to inclusion and exclusion criteria within the last ten years in Pubmed/Medline database, Science Direct, and Wiley Online Library with the keywords "Low-Carb Diet", "Low-Fat Diet", "Body Mass Index", "Lipid Levels", "Adipose Tissue", "Obese", and "Body Water". Discussion: Total body mass and fat mass decreased significantly after being given LCD intervention compared to LFD. The group that was given two dietary interventions also losing weight, but there was no changes in body water. In addition, negative effects were found from the LCD and LFD interventions such as constipation, fatigue, polyuria, nausea, vomiting, changes in appetite, and headaches. Kidney failure, ketosis, and premature coronary artery also occurred in the group that was given with LCD intervention. Conclusions: LCD and LFD interventions can affect body composition of people with obesity.

Trophic transfer of micro- and nanoplastics and toxicity induced by long-term exposure of nanoplastics along the rotifer (Brachionus plicatilis)-marine medaka (Oryzias melastigma) food chain

Microplastics (MPs) and nanoplastics (NPs) are emerging pollutants in the ocean, but their transfer and toxicity along the food chains are unclear. In this study, a marine rotifer (Brachionus plicatilis)-marine medaka (Oryzias melastigma) food chain was constructed to evaluate the transfer of polystyrene MPs and NPs (70 nm, 500 nm, and 2 μm, 2000 μg/L) and toxicity of 70 nm PS-NPs (0, 20, 200, and 2000 μg/L) on marine medaka after long-term food chain exposure. The results showed that the amount of 70 nm NPs accumulated in marine medaka was 1.24 μg/mg, which was significantly higher than that of 500 nm NPs (0.87 μg/mg) and 2 μm MP (0.69 μg/mg). Long-term food chain exposure to NPs caused microflora dysbiosis, resulting in activation of toll-like receptor 4 (TLR4) pathway, which induced liver inflammation. Moreover, NPs food chain exposure increased liver and muscle tissue triglyceride and lactate content, but decreased the protein, sugar, and glycogen content. NPs food chain exposure impaired reproductive function and inhibited offspring early development, which might pose a threat to the sustainability of marine medaka population. Overall, the study revealed the transfer of MPs and NPs and the effects of NPs on marine medaka along the food chain.

L-tryptophan effectively prevents fatty degeneration of rat pancreas

Alimentary obesity is a risk factor for the development of many pathophysiological conditions in various organs, including the pancreas. Thus, the study of mechanisms, clinical symptoms and ways to prevent the development of fatty degeneration of pancreas at obesity is a current direction of research. The aim of our work was to study the influence of L-tryptophan on the morphofunctional changes of the pancreas of rats with diet-induced obesity and to evaluate the possibility of its use for the prevention of the development of the gland fatty degeneration. The study was conducted in male Wistar rats, which were 3 months old at the experiment beginning. Histologic preparations were made from pancreas tissue samples using a standard method. Morphometric measurements were performed on digital images using “Image J” software. In biochemical studies, we determined concentration of glucose in blood serum and of triglycerides, lipids and cholesterol in pancreas tissue samples. It was found that rats fed a high-fat, high-carbohydrate diet showed marked sings of developing alimentary obesity. This was evidenced by a significant increase in the weight of visceral fat (by 147%) and obesity index (by 129%). The exposure of rats to a high-calorie diet resulted in the emergence of distinct signs indicating hypofunction in both the exocrine and, to a greater extent, endocrine sections of the pancreas. The administration of L-tryptophan reduced the intensity of accumulation of visceral fat and fat in the gland itself. This was evidenced by lower concentrations of lipids (by 53%) and triglycerides (by 32%) in the pancreatic tissue compared to high-calorie diet rats. In addition, L-tryptophan prevented an excessive decrease in the function of both the exocrine and endocrine parts of the gland from the harmful effects of dietary obesity. This may be of practical interest when using tryptophan and its derivatives in the clinic to prevent a decrease in gland activity in this pathology.