Increased Lipid Deposition Research Articles

Effects of feed nutrients on growth, development and the deposition of protein and fat in Tenebrio molitor larvae

Abstract An understanding of the impact of dietary nutritional composition on growth, development and composition of Tenebrio molitor larvae (mealworms) could help optimise production systems. Replicate containers of mealworms fed for 24 days on synthetic cellulose-based feeds containing different combinations of protein (casein, Cas), lipid (wheat germ oil, WGO), carbohydrate (glucose) and a mineral/vitamin premix (MV) were compared to a control diet of wheat bran (WB). Mealworms fed only cellulose (C) ceased to grow after 10 days, and did not pupate. Addition of casein alone did not restore growth but did induce pupation (much slower than in WB-fed worms). Mealworms fed C+Cas-based diets showed a marked increase in the relative proportion of body protein to fat, compared to those fed wheat bran. The addition of MV to the C+Cas diet restored growth and pupation, though not to the same level as WB. MV-fed worms maintained a significantly increased protein/fat composition. The further inclusion of WGO or WGO + glucose further increased growth, whilst WGO + glucose reduced pupation. Overall, the highest yield of protein (per container) was seen in the C+Cas+MV+WGO-fed mealworms, which was 50% higher than in the WB group (largely due to the decreased pupation rate). Furthermore, the lipid yield was 50% lower than in WB-fed mealworms. By contrast, the addition of glucose to this diet maintained a high protein yield but increased the lipid yield to similar levels as seen in WB-fed mealworms, with an associated significant increase in the relative proportion of the polyunsaturated fatty acids (PUFA), linoleic and α-linolenic acids. The results indicate that sources of protein, lipid, minerals and multivitamins are all required to maximize protein whilst decreasing lipid deposition in mealworms. However, the addition of glucose (and presumably other digestible carbohydrates) increased lipid deposition and specifically the PUFA content.

Dexamethasone synergizes with high-fat diet to increase lipid deposition in adipocytes.

Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

Comparative lipidomic and metabolomic profiling of mdx and severe mdx-apolipoprotein e-null mice

AbstractDespite its notoriously mild phenotype, the dystrophin-deficient mdx mouse is the most common model of Duchenne muscular dystrophy (DMD). By mimicking a human DMD-associated metabolic comorbidity, hyperlipidemia, in mdx mice by inactivating the apolipoprotein E gene (mdx-ApoE) we previously reported severe myofiber damage exacerbation via histology with large fibro-fatty infiltrates and phenotype humanization with ambulation dysfunction when fed a cholesterol- and triglyceride-rich Western diet (mdx-ApoEW). Herein, we performed comparative lipidomic and metabolomic analyses of muscle, liver and serum samples from mdx and mdx-ApoEW mice using solution and high-resolution-magic angle spinning (HR-MAS) 1H-NMR spectroscopy. Compared to mdx and regular chow-fed mdx-ApoE mice, we observed an order of magnitude increase in lipid deposition in gastrocnemius muscle of mdx-ApoEW mice including 11-fold elevations in -CH3 and -CH2 lipids, along with pronounced elevations in serum cholesterol, fatty acid, triglyceride and phospholipids. Hepatic lipids were also elevated but did not correlate with the extent of muscle lipid infiltration or differences in serum lipids. This study provides the first lipometabolomic signature of severe mdx lesions exacerbated by high circulating lipids and lends credence to claims that the liver, the main regulator of whole-body lipoprotein metabolism, may play only a minor role in this process.

Protective Effects of Exogenous Melatonin Administration on White Fat Metabolism Disruption Induced by Aging and a High-Fat Diet in Mice.

Obesity has emerged as a major risk factor for human health, exacerbated by aging and changes in dietary habits. It represents a significant health challenge, particularly for older people. While numerous studies have examined the effects of obesity and aging on fat metabolism independently, research on their combined effects is limited. In the present study, the protective action against white fat accumulation after a high-fat diet (HFD) exerted by exogenous melatonin, a circadian hormone endowed with antioxidant properties also involved in fat metabolism, was investigated in a mouse model. For this purpose, a battery of tests was applied before and after the dietary and melatonin treatments of the animals, including epididymal white adipose tissue (eWAT) histological evaluations, transcriptomic and lipidomic analyses, real-time PCR tests, immunofluorescence staining, Western blot, the appraisal of serum melatonin levels, and transmission electron microscopy. This study found that aged mice on a high-fat diet (HFD) showed increased lipid deposition, inflammation, and reduced antioxidant glutathione (GSH) levels compared to younger mice. Lipidomic and transcriptomic analyses revealed elevated triglycerides, diglycerides, ceramides, and cholesterol, along with decreased sphingomyelin and fatty acids in eWAT. The genes linked to inflammation, NF-κB signaling, autophagy, and lipid metabolism, particularly the melatonin and glutathione pathways, were significantly altered. The aged HFD mice also exhibited reduced melatonin levels in serum and eWAT. Melatonin supplementation reduced lipid deposition, increased melatonin and GSH levels, and upregulated AANAT and MTNR1A expression in eWAT, suggesting that melatonin alleviates eWAT damage via the MTNR1A pathway. It also suppressed inflammatory markers (e.g., TNF-α, NLRP3, NF-κB, IL-1β, and CEBPB) and preserved mitochondrial function through enhanced mitophagy. This study highlights how aging and HFD affect lipid metabolism and gene expression, offering potential intervention strategies. These findings provide important insights into the mechanisms of fat deposition associated with aging and a high-fat diet, suggesting potential intervention strategies.

Comparative study on the effects of high dietary levels of pectin and soybean oil on liver health and bile acid homeostasis in grass carp (Ctenopharyngodon idellus)

Liver disease in farmed grass carp (Ctenopharyngodon idellus) is a major issue with unclear mechanisms. High dietary fiber and fat may contribute. This study employed pectin and soybean oil as dietary fiber and fat sources, respectively, to evaluate their effects on liver disease in grass carp. Three diets (33.0 % crude protein) were made: control (5 % lipid; CON), high pectin (24 % pectin; HPD), high fat (15 % lipid; HFD). Juvenile grass carp (initial weight 24.1 g) were fed for 8 weeks. The HPD diet reduced growth and feed efficiency, whereas the HFD diet enhanced these parameters (P < 0.05). Both HPD and HFD expanded the scope of green in liver and deepened the color of bile. HPD decreased hepatosomatic index and liver lipid content, with atrophy and fibrosis. In contrast, HFD caused hepatocellular hypertrophy and increased lipid deposition. Gallbladder somatic index (GBSI) in both HPD and HFD groups was lower than in the CON group after 6 hours of fasting (P < 0.05). GBSI increased across all groups after 24 hours of fasting (P < 0.05), with the lowest values in the HPD group. In midgut and hindgut digesta, HPD group had higher total bile acid (TBA) content than CON group; HFD group's midgut also had higher TBA content. (P < 0.05). Serum TBA significantly decreased in the HPD group but increased in the liver (P < 0.05). Intestinal transporters asbt and ostα mRNA expression decreased in the HPD group, while asbt expression increased in the HFD group. Liver gene expression of inflammatory markers il-1β and il-8 was upregulated in both HPD and HFD groups (P < 0.05). These findings indicated high level of both pectin and soybean oil induce green liver syndrome and tissue damage, though the mechanisms differ, with HPD primarily causing cholestasis and HFD promoting lipid deposition.

Resistance Exercise Improves Glycolipid Metabolism and Mitochondrial Biogenesis in Skeletal Muscle of T2DM Mice via miR-30d-5p/SIRT1/PGC-1α Axis.

Exercise is a recognized non-pharmacological treatment for improving glucose homeostasis in type 2 diabetes (T2DM), with resistance exercise (RE) showing promising results. However, the mechanism of RE improving T2DM has not been clarified. This study aims to investigate the effects of RE on glucose and lipid metabolism, insulin signaling, and mitochondrial function in T2DM mice, with a focus on the regulatory role of miR-30d-5p. Our results confirmed that RE significantly improved fasting blood glucose, IPGTT, and ITT in T2DM mice. Enhanced expression of IRS-1, p-PI3K, and p-Akt indicated improved insulin signaling. RE improved glycolipid metabolism, as well as mitochondrial biogenesis and dynamics in skeletal muscle of T2DM mice. We also found that miR-30d-5p was upregulated in T2DM, and was downregulated after RE. Additionally, in vitro, over-expression of miR-30d-5p significantly increased lipid deposition, and reduced glucose uptake and mitochondrial biogenesis. These observations were reversed after transfection with the miR-30d-5p inhibitor. Mechanistically, miR-30d-5p regulates glycolipid metabolism in skeletal muscle by directly targeting SIRT1, which affects the expression of PGC-1α, thereby influencing mitochondrial function and glycolipid metabolism. Taken together, RE effectively improves glucose and lipid metabolism and mitochondrial function in T2DM mice, partly through regulating the miR-30d-5p/SIRT1/PGC-1α axis. miR-30d-5p could serve as a potential therapeutic target for T2DM management.

Neurotoxic and developmental effects of scented incense stick smoke: Network toxicology and zebrafish model study

Burning incense sticks is a traditional practice in many cultures, especially in Southeast Asia. While it is often regarded as sacred and beneficial, modern incense sticks contain various chemicals that can pose health risks. A GCMS analysis of the ICS revealed potential compounds. Network toxicology revealed that ICS contains compounds violating Lipinski's rule of five, leading to potential neurotoxic effects. Key pathways affected include neuroactive ligand-receptor interaction and calcium signaling, associated with neurodegenerative diseases like Parkinson's and Alzheimer's. Significant genes involved are STAT3, BCL2, and MTOR, emphasizing the chemical hazards of ICS exposure. We investigated the toxicity of ICS using zebrafish (Danio rerio) embryos as a mode. ICS exposure resulted in a dose-dependent increase in toxicity. High concentrations (7 and 14 µg/ml) led to immediate mortality, while lower concentrations (0.1, 0.3, 0.5, and 1 µg/ml) caused developmental defects such as yolk sac edema, skeletal malformations, and pericardial edema. Mortality rates increased with higher concentrations, confirming dose-dependent ICS exposure caused hypoactive locomotion, with reduced distance traveled and velocity toxicity. Higher concentrations of ICS led to increased ROS levels and cellular damage, as evidenced by enhanced staining levels. A dose-dependent increase in lipid peroxidation (DPPP assay) and lipid accumulation (Nile red assay) was observed. Higher ICS concentrations led to significant oxidative damage to lipids and increased lipid deposition. Enzymatic assays showed that ICS exposure significantly decreased the activities of antioxidant enzymes SOD and CAT, indicating impaired antioxidant defense, while increasing LDH activity, signaling tissue damage and cytotoxicity. Gene expression analysis revealed downregulation of SOD1 and CAT genes, upregulation of inflammatory genes TNF-α and IL-1β, and increased expression of the apoptotic gene p53 with decreased expression of Bcl-2 and BDNF. These findings highlight ICS's potential to cause oxidative stress, inflammation, apoptosis, and neurodevelopmental impairments.

Reexamining the Role of Pulmonary Lipids in the Pathogenesis of Pulmonary Fibrosis.

Pulmonary fibrosis (PF) can be idiopathic or driven by a specific insult, genetic susceptibility, or disease process. Inflammation plays a role in the pathophysiology, the extent of which remains a longstanding topic of debate. More recently, there has been increasing interest in a potential inciting role for aberrant lipid metabolism. Lipids are essential for the structure and function of all cell membranes, but specifically in the lung for surfactant composition, intra- and intercellular lipid mediators, and lipofibroblasts. Clinically, there is evidence of increased lipid deposition in the subpleural space and at a whole-lung tissue level in PF. There is evidence of increased parenchymal lipid deposition and abnormal mediastinal fat shape on chest computed tomography. A protective role for cholesterol-lowering drugs, including statins and ezetimibe, has been described in PF. At a cellular level, fatty acid, phospholipid, and glucose metabolism are disordered, as is the production of lipid mediators. Here we put forward the argument that there is substantive clinical and biological evidence to support a role for aberrant lipid metabolism and lipid mediators in the pathogenesis of PF.

Effect of Epigenetic Inhibitors on Adipogenesis in Human Periodontal Ligament Stem Cells

Histone H3 lysine 9 acetylation is a crucial epigenetic mark in mesenchymal stem cell differentiation processes like adipogenesis. This study aimed to evaluate the effect of epigenetic inhibitors on adipogenesis in human periodontal ligament stem cells, using histone deacetylase inhibitors such as valproic acid and trichostatin A. The cells were treated independently with 8 mM valproic acid and 100 nM trichostatin A for 72 hours to inhibit class I histone deacetylases. Subsequently, the cells underwent adipogenic induction for 28 days. Morphology and intracellular lipid deposition were analyzed using Oil-Red oil staining. Protein extracts were prepared on days 0 and 28 to analyze histone H3 lysine 9 acetylation levels via Western blot. Our results demonstrated that cells treated with either VPA or TSA showed, on average, a 1.275-fold increase in lipid deposition during the adipogenic process, with no significant differences between the treatments compared to the control group. Further, by day 28, histone H3 lysine 9 acetylation levels were 1.43 times higher in cells treated with valproic acid and 2.52 times higher in those treated with trichostatin A.These findings suggest that the inhibitors could have differential effects on chromatin remodeling in different regions by increasing acetylation, contributing indistinctly to lipid deposition due to the greater expression of genes associated with the adipogenic phenotype.

Knockdown of the Clock gene in the liver aggravates MASLD in mice via inhibiting lipophagy.

The increased global prevalence of metabolic dysfunction-associated steatohepatitis (MASLD) has been closely associated with chronic disorders of the circadian clock. Herein, we investigate the role of Clock, a core circadian gene, in the pathogenesis of MASLD. Wild-type (WT) and liver-specific Clock knockdown (Clock-KD) mice were fed a Western diet for 20weeks to induce MASLD. A cellular MASLD model was established by treating AML12 cells with free fatty acids and the effects of Clock knockdown were examined following transfection with Clock siRNA. Increased lipid deposition and more severe steatohepatitis and fibrosis were observed in the livers of Western diet-fed but not normal chow diet-fed Clock-KD mice after 20weeks compared to WT mice. Moreover, the Clock gene was found to be significantly downregulated in WT MASLD mice. The Clock gene was shown to regulate the expression of lipophagy-related proteins (LC3B, P62, RAB7, and PLIN2) in vivo and in vitro. Knockdown of Clock was found to inhibit lipophagy resulting in increased accumulation of lipid droplets in the mouse liver and AML12 cells. Interestingly, the CLOCK protein was shown to interact with P62. However, knockdown of the Clock gene did not promote transcription of the P62 gene but suppressed degradation of the P62 protein during lipophagy in AML12 cells. The hepatic Clock gene regulates lipophagy and affects lipid droplet deposition in liver cells, and thus plays a critical role in the development of MASLD induced by a Western diet.

Vascular Endothelial Growth Factor-B Blockade with CSL346 in Diabetic Kidney Disease: A Phase 2A Randomized Controlled Trial.

Increased vascular endothelial growth factor B (VEGF-B) expression in patients with diabetic kidney disease (DKD) is associated with increased lipid deposition in glomerular podocytes. Reducing VEGF-B activity in animal models of DKD using an anti-VEGF-B antibody improved histological evidence of glomerular injury and reduced albuminuria; effects attributed to prevention of ectopic lipid deposition in the kidney. CSL346 is a novel humanized monoclonal antibody that binds VEGF-B with high affinity. Targeting VEGF-B in patients with type 2 diabetes mellitus may improve DKD progression markers. An international, randomized, double-blind, placebo-controlled, phase 2a study (NCT04419467) assessed CSL346 (8 mg/kg or 16 mg/kg subcutaneously every 4 weeks for 12 weeks) in participants with type 2 diabetes mellitus and a urinary albumin-to-creatinine ratio (UACR) ≥150 mg/g (17.0 mg/mmol), and eGFR >20 mL/min/1.73m2. Efficacy, safety/tolerability, pharmacokinetics, and pharmacodynamics of CSL346 were evaluated. The primary analysis compared the change from baseline in log-transformed UACR between the two CSL346 dose groups combined versus placebo at Week 16. In total, 114 participants were randomized. CSL346 did not significantly reduce UACR compared with placebo at Week 16 (combined CSL346 group difference from placebo 95% confidence interval]: 4.0% [-14.7, 26.8]). Furthermore, no effect was seen in participant subgroups (degree of kidney impairment or sodium-glucose cotransporter 2 [SGLT2] inhibitor use) or on urinary biomarkers reflecting proximal tubular injury. CSL346 was generally well tolerated; however, diastolic blood pressure was significantly higher with CSL346 16 mg/kg versus placebo from Week 2 onwards, with differences ranging from +3.8 to +5.3 mmHg (P = 0.002 at Week 16). CSL346 did not reduce UACR compared with placebo at 16 weeks in participants with type 2 diabetes mellitus and DKD, and was associated with an increase in diastolic blood pressure.

Lack of alpha CGRP exacerbates the development of atherosclerosis in ApoE-knockout mice

The effects of calcitonin gene-related peptide (CGRP) on atherosclerosis remain unclear. We used apolipoprotein E-deficient (ApoE−/−) mice to generate double-knockout ApoE−/−:CGRP−/− mice lacking alpha CGRP. ApoE−/−:CGRP−/− mice exhibited larger atherosclerotic plaque areas, peritoneal macrophages with enhanced migration functions, and elevated levels of the inflammatory cytokine tumor necrosis factor (TNF)-⍺. Thus, we also explored whether inhibiting TNF-⍺ could improve atherosclerosis in ApoE−/−:CGRP−/− mice by administering etanercept intraperitoneally once a week (5 mg/kg) alongside a high-fat diet for 2 weeks. This treatment led to significant reductions in aortic root lesion size, atherosclerotic plaque area and macrophage migration in ApoE−/−:CGRP−/− mice compared with mice treated with human IgG (5 mg/kg). We further examined whether results observed in ApoE−/−:CGRP−/− mice could similarly be obtained by administering a humanized monoclonal CGRP antibody, galcanezumab, to ApoE−/− mice. ApoE−/− mice were subcutaneously administered galcanezumab at an initial dose of 50 mg/kg, followed by a dose of 30 mg/kg in the second week. Galcanezumab administration did not affect systolic blood pressure, serum lipid levels, or macrophage migration but led to a significant increase in lipid deposition at the aortic root. These findings suggest that alpha CGRP plays a critical role in inhibiting the progression of atherosclerosis.

Food emulsifiers aggravate inflammation and oxidative stress induced by food contaminants in zebrafish

Food emulsifiers like glycerol monostearate (G) and Tween 80 (TW) are commonly used to help formation and maintain stability of emulsions. However, certain food contaminants and emulsifiers often co-occur in the same food item due to food culture and cooking methods. For this reason, the present study investigated interaction of toxic effect of emulsifiers (G and TW) and process contaminants (acrylamide (AA) and benzo [a]pyrene (BAP)) on zebrafish. Adult zebrafish were exposed to emulsifiers, food contaminants, or the combination through diet for 2 h and 7 days. Oxidative stress and inflammation caused by food contaminants were increased when food emulsifiers were present. These combined treatments also induced more severe morphological changes than the contaminant alone treatments. In the gut, disruption of villi structure and increased number of goblet cells was observed and in the liver there were increased lipid deposition, infiltration of immune cells, glycogen depletion and focal necrosis. Increased accumulation of AA and BAP in the liver and gut were detected after addition of emulsifiers, suggesting that emulsifiers can enhance absorption of diet-borne contaminants. Our results showed food emulsifiers and contaminants can interact synergistically and increase risk.

A short-term rodent model for non-alcoholic steatohepatitis induced by a high-fat diet and carbon tetrachloride.

Several models of mice-fed high-fat diets have been used to trigger non-alcoholic steatohepatitis and some chemical substances, such as carbon tetrachloride. The present study aimed to evaluate the joint action of a high-fat diet and CCl4 in developing a short-term non-alcoholic steatohepatitis model. C57BL6/J mice were divided into two groups: standard diet-fed (SD), the high-fat diet-fed (HFD) and HFD + fructose-fed and carbon tetrachloride (HFD+CCl4). The animals fed with HFD+CCl4 presented increased lipid deposition compared with both SD and HFD mice. Plasma cholesterol was increased in animals from the HFD+CCl4 group compared with the SD and HFD groups, without significant differences between the SD and HFD groups. Plasma triglycerides showed no significant difference between the groups. The HFD+CCl4 animals had increased collagen deposition in the liver compared with both SD and HFD groups. Hydroxyproline was also increased in the HFD+CCl4 group. Liver enzymes, alanine aminotransferase and aspartate aminotransferase, were increased in the HFD+CCl4 group, compared with SD and HFD groups. Also, CCl4 was able to trigger an inflammatory process in the liver of HFD-fed animals by promoting an increase of ∼2 times in macrophage activity, ∼6 times in F4/80 gene expression, and pro-inflammatory cytokines (IL-1b and TNFa), in addition to an increase in inflammatory pathway protein phosphorylation (IKKbp). HFD e HFD+CCl4 animals increased glucose intolerance compared with SD mice, associated with reduced insulin-stimulated AKT activity in the liver. Therefore, our study has shown that short-term HFD feeding associated with fructose and CCl4 can trigger non-alcoholic steatohepatitis and cause damage to glucose metabolism.

The Effect of a High-Fat Western Diet on Diabetic Nephropathy and the Pathogenesis of Type 2 Diabetes

The high-fat Western diet is a key contributor to the growing rate of obesity, which has become a global health concern. Additionally, obesity increases the risk of developing metabolic syndrome which leads to a range of chronic illnesses like diabetes, heart disease, and stroke. Diabetic Nephropathy (DN) is a complication prevalent in one-third of people with Type 2 Diabetes and leads to End Stage Renal Disease. The aim of this study was to assess how a high-fat Western diet impacts diabetic severity and renal, cardiovascular, and hepatic injury, in a rodent model of type 2 Diabetes. We used aged (&gt;38 weeks old, with severe renal disease) and young (12 weeks old, prior to major kidney damage) male and female Type 2 Diabetic Nephropathy (T2DN) rats, a non-obese diabetic animal model, and placed them on either normal (NFD) or high fat (HFD) calorically balanced diets for 12 weeks. Urine sampling and glucose tolerance tests (GTT) were assessed every 3 weeks. All rats on the HFD had significantly increased total body weights (TBW). However, average caloric intake over the 12 weeks was not significantly different in young males and females or in old males, while the aged HFD females had a significant increase (52.18 ± 1.536 vs 67.43 ± 0.4682 kcal/g, p=0.0001). The HFD had no effect on female GTT curves or fasting blood glucose in either age group. In contrast, the HFD males’ glucose intolerance and fasting blood glucose levels increased progressively and became significantly different between diets by week 9 (old: 204.5 ± 10.8 vs 284.4 ± 15.8 mg/dL, p=0.003, young: 193.3 ± 9.497 vs 257.5 ± 17.19 mg/dL, p=0.02). The HFD did not affect urine output or 2-kidney/TBW ratios in both sexes, while heart weight/TBW ratios in females were significantly reduced on the HFD in both age groups. Studies are ongoing in young animals; however, old animals revealed a significant increase in lipid deposits in the liver of HFD group for both males and females. There were no significant changes in circulating cholesterol and triglyceride levels between diets; however, there was a trend to increased triglycerides in females on HFD (p=0.051). The liver function panel showed a significant increase in ALP liver enzyme in the HFD group of both sexes. Picrosirius red-stained heart tissue showed increased fibrosis in the HFD aged males. Microbiome analysis revealed a significant decrease in gut microbiota alpha diversity in males on HFD, while no significant changes were observed in females between diets. Ongoing studies will quantify renal damage, including cortical fibrosis, medullary protein casts, glomerular damage, albuminuria, and KIM-1 staining, as well as lipidemia and heart fibrosis resulting from the HFD for both old and young animals. In conclusion, the HFD appears to have a more deleterious effect on glucose handling in both old and young T2DN males than in female rats; however, further studies are warranted to validate this effect. R01 DK129227, R01 DK135644, R00 HL153686. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Molecular characterization of vascular endothelial growth factor b from spotted sea bass (Lateolabrax maculatus) and its potential roles in decreasing lipid deposition

Vascular endothelial growth factor B (VEGFB), a member of the VEGF family, exhibits limited angiogenic activity in mammals but plays an unexpected role in targeting lipids to peripheral tissues. However, its role in lipid metabolism in fish is unknown. In this study, the vegfb gene was cloned and characterized from spotted sea bass (Lateolabrax maculatus). It encodes 254 amino acids and possesses the typical characteristics of the Vegfb family, demonstrating high homology with those from other vertebrate species. The vegfb gene exhibits the highest expression levels in the liver, followed by the gills, intestine, and adipose tissues in spotted sea bass. In vivo, high-lipid diets decreased vegfb expression and increased lipid deposition in liver of fish. In vitro, palmitic acid + oleic acid treatment or vegfb knockdown significantly increased TG and TC contents, promoting lipid droplet deposition in hepatocytes. Vegfb overexpression has the opposite effects, inhibiting lipid deposition and downregulating fatty acid transport and adipogenesis genes. In contrast, the vegfb knockdown significantly upregulated the expression levels of c/ebpα, plin2, and dgat1 (P < 0.05). These results demonstrate that Vegfb may play an important role in reducing lipid deposition by regulating fatty acid transport and adipogenesis in the hepatocytes of spotted sea bass.

Characterization and function of PTEN-induced putative kinase 1 (PINK1) in process of Zinc alleviates hepatic lipid deposition of yellow catfish (Pelteobagrus fulvidraco)

PTEN-induced putative kinase 1 (PINK1) is a key regulator of mitophagy, however, the relevant information remains poorly understood on aquatic animals. Here, a PINK1 gene was cloned, characterized and functionally studied in yellow catfish. PINK1 encoded a protein containing 570 amino acids, 2 functional domains. High fat (15.66%) fed fish showed a downregulation trend of liver PINK1 expression than that of normal fat (10.14%) group, and was reversed by the addition of Zn. In the in vitro study, high fat (HF) can increase lipid deposition and decrease by addition Zn (HFZ) in hepatocytes, whereas above phenomena reversed by overexpression/interference of PINK1, respectively. In addition, the addition of Zn can significantly affect mitochondrial activity, increase mitophagy, and improve the antioxidant activity of hepatocytes. Together, these findings illustrated that yellow catfish PINK1 is conserve, and it participated in mitochondria control of fish. These findings indicate Zn could alleviate high fat-induced hepatic lipid deposition of fish by activating PINK1-mediated mitophagy and provide basis for further exploring new approach for decreasing lipid deposition in fish products during aquaculture.

Perilipin2 inhibits the replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions.

Chronic hepatitis B virus (HBV) infection is often associated with increased lipid deposition in hepatocytes. However, when combined with non-alcoholic fatty liver disease or hyperlipidemia, it tends to have a lower HBV deoxyribonucleic acid (DNA) load. The relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms are not well understood. To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms. 1603 HBsAg-seropositive patients were included in the study. We first explored the relationship between patients' lipid levels, hepatic steatosis, and HBV DNA load. Also, we constructed an HBV infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on HBV DNA replication in vitro. By knocking down and overexpressing Plin2, we observed whether Plin2 regulates autophagy and HBV replication. By inhibiting both Plin2 and cellular autophagy under high lipid stimulation, we examined whether the Plin2-autophagy pathway regulates HBV replication. The results revealed that serum triglyceride levels, high-density lipoprotein levels, and hepatic steatosis ratio were significantly lower in the HBV-DNA high load group. Logistic regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with HBV-DNA load. Stratified analysis by HBeAg showed significant negative correlations between HBV-DNA load and hepatic steatosis ratio in both HBeAg-positive and HBeAg-negative groups. An in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between HBV-DNA load and lipid metabolism. The results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg, HBeAg, and HBV DNA load. Western blot and polymerase chain reaction analysis showed that fatty acid stimulation significantly induced Plin2 protein expression and inhibited the expression of hepatocyte autophagy proteins. Inhibition of Plin2 protein expression under fatty acid stimulation reversed the reduction in HBsAg and HBeAg expression and HBV DNA load induced by fatty acid stimulation and the inhibition of cellular autophagy. Knocking down Plin2 and blocking autophagy with 3-methyladenine (3-MA) inhibited HBV DNA replication. In conclusion, lipid metabolism is a significant factor affecting HBV load in patients with HBV infection. The in vitro experiments established that fatty acid stimulation inhibits HBV replication via the Plin2-autophagy pathway.

Selection on the promoter regions plays an important role in complex traits during duck domestication

BackgroundIdentifying the key factors that underlie complex traits during domestication is a great challenge for evolutionary and biological studies. In addition to the protein-coding region differences caused by variants, a large number of variants are located in the noncoding regions containing multiple types of regulatory elements. However, the roles of accumulated variants in gene regulatory elements during duck domestication and economic trait improvement are poorly understood.ResultsWe constructed a genomics, transcriptomics, and epigenomics map of the duck genome and assessed the evolutionary forces that have been in play across the whole genome during domestication. In total, 304 (42.94%) gene promoters have been specifically selected in Pekin duck among all selected genes. Joint multi-omics analysis reveals that 218 genes (72.01%) with selected promoters are located in open and active chromatin, and 267 genes (87.83%) with selected promoters were highly and differentially expressed in domestic trait-related tissues. One important candidate gene ELOVL3, with a strong signature of differentiation on the core promoter region, is known to regulate fatty acid elongation. Functional experiments showed that the nearly fixed variants in the top selected ELOVL3 promoter in Pekin duck decreased binding ability with HLF and increased gene expression, with the overexpression of ELOVL3 able to increase lipid deposition and unsaturated fatty acid enrichment.ConclusionsThis study presents genome resequencing, RNA-Seq, Hi-C, and ATAC-Seq data of mallard and Pekin duck, showing that selection of the gene promoter region plays an important role in gene expression and phenotypic changes during domestication and highlights that the variants of the ELOVL3 promoter may have multiple effects on fat and long-chain fatty acid content in ducks.

Aging and Metabolic Reprogramming of Adipose-Derived Stem Cells Affect Molecular Mechanisms Related to Cardiovascular Diseases.

We performed a systematic search of the PubMed database for English-language articles related to the function of adipose-derived stem cells in the pathogenesis of cardiovascular diseases. In preclinical models, adipose-derived stem cells protected arteries and the heart from oxidative stress and inflammation and preserved angiogenesis. However, clinical trials did not reiterate successful treatments with these cells in preclinical models. The low success in patients may be due to aging and metabolic reprogramming associated with the loss of proliferation capacity and increased senescence of stem cells, loss of mitochondrial function, increased oxidative stress and inflammation, and adipogenesis with increased lipid deposition associated with the low potential to induce endothelial cell function and angiogenesis, cardiomyocyte survival, and restore heart function. Then, we identify noncoding RNAs that may be mechanistically related to these dysfunctions of human adipose-derived stem cells. In particular, a decrease in let-7, miR-17-92, miR-21, miR-145, and miR-221 led to the loss of their function with obesity, type 2 diabetes, oxidative stress, and inflammation. An increase in miR-34a, miR-486-5p, and mir-24-3p contributed to the loss of function, with a noteworthy increase in miR-34a with age. In contrast, miR-146a and miR-210 may protect stem cells. However, a systematic analysis of other noncoding RNAs in human adipose-derived stem cells is warranted. Overall, this review gives insight into modes to improve the functionality of human adipose-derived stem cells.