Lipid Utilization Research Articles

Onset of circadian rhythmicity in the brain of Atlantic salmon is linked to exogenous feeding.

An organism's biological processes are adapted to and driven by rhythmicity in the natural environment and periodicity of light is one of the most influential factors. In a developing organism, the onset of circadian rhythmicity might indicate the time point of functional necessity for aligning processes to the environment. Here, the circadian clock mechanism has been studied in the developing brain of Atlantic salmon (Salmo salar), by comparing the endogenous feeding alevin, independent on the environment for nutritional supply, to the exogenous feeding fry, dependent on the light period for detecting and catching prey. The results showed that while only a few clock genes were cyclic in the yolk sac alevins, many of the clock genes and genes of the circadian rhythm pathway cycled significantly in the feeding fry. Few genes were differentially expressed between time points in the circadian sampling series during the yolk sac stage, but several hundred genes were found differentially expressed in the first feeding stage. Genes important for cell cycle progression were cyclic or differentially expressed between time points after exogenous feeding, indicating a clock-controlled cell cycle at this stage. The expression of important genes in the melatonin synthesis were also cyclic in the feeding fry with an acrophase in the transition between light and dark or in darkness. Analyzing the impact of exogenous feeding on the developing brain supported a shift from utilization of proteins and lipids in the yolk to utilization and allocation of dietary energy and nutrients. Taken together, the life history transition related to onset of exogenous feeding is linked to the establishment of a persistent circadian rhythmicity in the salmon brain, which needs to be synchronized to light-dark cycles to enable the fry to search and capture feed.

Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis.

The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

Effects of the Supplementation of Lysophospholipid in Low‐Lipid Diets on Juvenile Pacific White Shrimp

The shortage of lipid sources has been a limiting factor of the aqua‐feed industry. Lysophospholipid (LPL) is a highly efficient lipid emulsifier, which may help improve lipid utilization efficiency and thus spare the dietary lipid. This study aimed to evaluate the effects of LPL on growth performance, fatty acid composition, and lipid metabolism of juvenile Litopenaeus vannamei (averagely, 2.4 g). Five diets were prepared: a control diet with 6.5% lipid, the control diet supplemented with 0.05% or 0.1% LPL (0.05% LPL and 0.1% LPL), a moderately low‐lipid (MLL) diet supplemented with 0.05% LPL (0.05% LPL‐MLL), and an extremely low‐lipid (ELL) diet supplemented with 0.1% LPL (0.1% LPL‐ELL). Each dietary group had triplicate tanks (30 shrimp in each tank). The feeding experiment lasted 8 weeks. Compared with the control group, the addition of 0.05% LPL promoted the growth by 9.95%; diet 0.05% LPL‐MLL resulted in a comparable growth to the control, but diet 0.1% LPL‐ELL tended to adversely affect the growth. Dietary LPL had little effect on the whole‐body proximate composition. The content of 18:2n−6 and 18:3n−3 was significantly higher in the 0.05% LPL group compared to the control. The 20:5n−3 content was the highest in the 0.05%LPL‐MLL group. In addition, the 0.05% LPL and 0.1% LPL group increased the plasma high‐density lipoprotein‐cholesterol content. Meanwhile, all LPL groups reduced the low‐density lipoprotein‐cholesterol content. The addition of LPL significantly regulated the messenger RNA (mRNA) expression of genes related to cholesterol homeostasis, such as ldlr, srb1, abca1, and abcg8. In conclusion, dietary supplementation with 0.05% LPL tended to promote shrimp growth and can spare 15% dietary lipid. However, when the dietary lipid content decreased from 6.5% to an extremely low level of 4.8%, dietary LPL was ineffective to spare lipids. This was the first study to validate the lipid‐sparing effect of dietary LPL in shrimp.

Role of Apolipoproteins in Neurodegenerative Diseases

Since lipids are insoluble in water, they are carried in the blood as particles called lipoproteins. Lipoproteins consisting of lipids and proteins are multicomponent complexes. The classification of lipoproteins, which are divided into several main groups such as low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL) and chylomicrons, is based on their density, size, lipid and apolipoprotein content. Apolipoproteins are the protein component of lipoproteins that carry lipids from the blood to various tissues of the body for metabolism and utilisation. Apolipoproteins play an important role in lipid metabolism. They regulate many metabolic enzymes and interact with lipoprotein receptors. Numerous studies have shown that apolipoprotein phenotype, different allelic polymorphism and apolipoprotein gene mutation can affect metabolism and utilisation of blood lipids and consequently trigger the onset and development of atherosclerosis, hyperlipidaemia, cerebrovascular and cardiovascular diseases. Furthermore, apolipoproteins have been associated with neurodegenerative diseases and different apolipoprotein polymorphisms have been evaluated as risk factors or protective agents in different neurodegenerative diseases. This review presents evidence from some studies linking apolipoproteins with Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration disease.

Growth Performance and Nutrient Utilizations of Heterobranchus bidorsalis (Geoffory Saint Hilaire, 1809) Fed on Fermented Sorghum Bran Meal Diets

The growth of aquaculture faces a high cost of feed which is about 60% to 75% of total production costs. An effort should be made to increase the profit by reducing the cost of feed as minimal as possible. This study investigated the growth performance and nutrient utilizations of Heterobranchus bidorsalis fed on fermented sorghum bran meal diets. sorghum bran was fermented at 10% moisture for seven days and samples for proximate analysis were collected on the first, fourth and seventh day. The highest crude protein was obtained in seventh day fermentation with 17.59±1.53% and the lowest was obtained in the zero day (control) with 10.53±1.53. Four isoproteic diets (40% crude protein) were formulated at 25%, 50%, 75% and 100% inclusion level to replace maize meal. The diets were fed to H.bidorsalis for twelve weeks. The experimental fish were fed 5% body weight throughout the experiment. The results obtained from the feeding trial showed that the fish fed on 100% inclusion level shows significance difference (p<0.05) in mean weight gain compared to fish fed on other diets. The highest mean weight gain (MWG) was obtained in the fish fed on 100% inclusion level diet (D5) with 43.39±1.86g and the lowest was obtained in control diet (D1) with 28.97±0.54g. The highest Average Daily Growth (ADG) and Specific Growth Rate (SGR) were obtained in the fish fed on (D5) with 0.52±0.56 and 1.07±0.64 while the lowest were obtained in the fish fed on control diet with 0.35±0.51 and 0.91±0.65 respectively. The nutrient utilizations showed significant difference (p<0.05) in fish fed on (D5) compared to others. The highest feed conversion ratio (FCR) was obtained in fish fed on (D5) with 0.48±0.16 and the lowest was obtained in control with 0.41±0.24. The highest protein intake (PI), protein rating (PR) and protein growth rate (PGR) were obtained in the fish fed on (D5) with 43.12±1.27, 0.52±0.72 and 1.04±0.71 while the lowest were obtained in the fish fed on control with 29.99±0.71, 0.35±0.45 and 1.00±0.53 respectively. The highest Protein Efficiency Ratio (PER) was obtained in the fish fed on (D5) with 1.01±0.07 and the lowest was obtained in the fish fed 50% inclusion level diet (D3) with 0.95±0.62. The highest Apparent Net Protein Utilization (ANPU) and Apparent Net Lipid Utilization (ANLU) were recorded in the fish fed on (D5) with 23.35±0.92 and 161.22±0.26 while the lowest were recorded in the fish fed on (D1) with 14.68±1.05 and 131.27±0.74 respectively. This study revealed the positive effects of incorporating fermented Sorghum bran meal into the diet of H. bidorsalis.

Saturated fatty acids stimulate cytokine production in tanycytes via the PP2Ac-dependent signaling pathway

The hypothalamic tanycytes are crucial for free fatty acids (FFAs) detection, storage, and transport within the central nervous system. They have been shown to effectively respond to fluctuations in circulating FFAs, thereby regulating energy homeostasis. However, the precise molecular mechanisms by which tanycytes modulate lipid utilization remain unclear. Here, we report that the catalytic subunit of protein phosphatase 2 A (PP2Ac), a serine/threonine phosphatase, is expressed in tanycytes and its accumulation and activation occur in response to high-fat diet consumption. In vitro, tanycytic PP2Ac responds to palmitic acid (PA) exposure and accumulates and is activated at an early stage in an AMPK-dependent manner. Furthermore, activated PP2Ac boosts hypoxia-inducible factor-1α (HIF-1α) accumulation, resulting in upregulation of an array of cytokines. Pretreatment with a PP2Ac inhibitor, LB100, prevented the PA-induced elevation of vascular endothelial growth factor (VEGF), fibroblast growth factor 1 (FGF1), hepatocyte growth factor (HGF), and dipeptidyl peptidase IV (DPPIV or CD26). Our results disclose a mechanism of lipid metabolism in tanycytes that involves the activation of PP2Ac and highlight the physiological significance of PP2Ac in hypothalamic tanycytes in response to overnutrition and efficacious treatment of obesity.

Lack of vitamin D signalling shifts skeletal muscles towards oxidative metabolism.

Mice lacking vitamin D receptor (VDR) exhibit a glycogen storage disorder, disrupting carbohydrate utilization in muscle. Here, we asked if the defective carbohydrate metabolism alters the fat utilization by the skeletal muscles of vdr-/- mice. To check the effect of high-fat-containing diets on muscle mass and metabolism of vdr-/- mice, we subjected them to two different milk fat-based diets (milk fat diet with 60% of energy from milk fat and milk-based diet [MBD] with 37% of energy from milk fat) and lard-based high-fat diet (HFD) containing 60% of energy from lard fat. Skeletal muscles and pancreas from these mice were analysed using RNA sequencing, quantitative reverse transcription polymerase chain reaction and western blot to understand the changes in signalling and metabolic pathways. Microscopic analyses of cryosections stained with haematoxylin and eosin, BODIPY, succinate dehydrogenase and periodic acid-Schiff reagent were performed to understand changes in morphology and metabolism of muscle fibres and pancreatic islets. Transcriptomic analyses showed that the skeletal muscles of vdr-/- mice exhibit upregulation of the fatty acid oxidation pathways, suggesting a shift towards increased lipid utilization even in a carbohydrate-enriched regular chow diet (chow). Two different milk fat-enriched diets restored body weight (12.01±0.33g in chowvs. 17.99±0.62g in MBD) and muscle weights (38.58±3.84mg in chow vs. 110.72±1.96mg in MBD for gastrocnemius [GAS]) of vdr-/- mice. Muscle ATP levels (0.56±0.18μmol in chow vs. 1.48±0.08μmol in MBD) and protein synthesis (0.25±0.04A.U. in chow vs. 2.02±0.06A.U. in MBD) were upregulated by MBD. However, despite increasing muscle energy levels, HFD failed to restore the muscle mass and cross-sectional area to that of wild-type (WT) mice (104.95±2.6mg for WT mice on chow vs. 77.26±1.7mg for vdr-/- mice on HFD for GAS). Moreover, HFD disrupted glucose homeostasis in vdr-/- mice, while MBD restored it. We further analysed insulin response and pancreatic insulin levels of these mice to show that HFD led to reduced insulin levels in pancreatic beta cells of vdr-/- mice (mean intensity of 1.5×10-8 for WT mice on chow vs. 4.3×10-9 for vdr-/- mice on HFD). At the same time, MBD restored glucose-stimulated pancreatic insulin response (mean intensity of 9.2×10-9 ). Skeletal muscles of vdr-/- mice are predisposed to utilize fatty acids as their primary energy source to circumvent their defective carbohydrate utilization. Thus, HFDs could restore energy levels in the skeletal muscles of vdr-/- mice. This study reveals that when mice are subjected to a lard-based HFD, VDR signalling is essential for maintaining insulin levels in pancreatic islets. Our data show a critical role of VDR in muscle metabolic flexibility and pancreatic insulin response.

Fatty acid translocase (FAT/CD36) in silver pomfret (Pampus argenteus): Molecular cloning and functional characterization

Understanding the mechanisms of lipid transport and metabolism in fish is crucial to enhance dietary lipid utilization. Here, fatty acid translocase (CD36) gene was characterized in silver pomfret (Pampus argenteus). The open reading frame of silver pomfret cd36 gene was 1395 bp, encoding 464 amino acids. The silver pomfret CD36 protein contained typical transmembrane regions and N-glycosylation modification sites, and was localized to the cytomembrane. The cd36 gene was ubiquitously expressed in all tested tissues, with the highest expression observed in brain tissue. In vivo, both fasting and short-term high-fat feeding could increase cd36 expression in intestinal tissue. In vitro, cd36 expression was induced by palmitic acid, oleic acid, linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid treatment in intestinal tissue. Furthermore, dual-luciferase reporter assay results indicated that peroxisome proliferator-activated receptor gamma (PPARγ) could enhance cd36 promoter activity, and the co-expression of cd36 and pparγ was observed in EPA-incubated intestine, suggesting that EPA may regulate the expression of cd36 via PPARγ to maintain the homeostasis of intestinal lipid metabolism in silver pomfret. These results highlighted the crucial role of CD36 in silver pomfret, and suggested that the cd36 expression may be regulated by PPARγ. This study could contribute to a greater understanding of lipid metabolism and the development of effective strategies for nutrient requirements in fish.

The Molecular Mechanisms of Fuel Utilization during Exercise.

Exercise is widely recognized for its positive impact on human health and well-being. The process of utilizing substrates in skeletal muscle during exercise is intricate and governed by complex mechanisms. Carbohydrates and lipids serve as the primary fuel sources for skeletal muscle during exercise. It is now understood that fuel selection during exercise is not solely determined by physical activity itself but is also influenced by the overall metabolic state of the body. The balance between lipid and carbohydrate utilization significantly affects exercise capacity, including endurance, fatigue, and overall performance. Therefore, comprehensively understanding the regulation of substrate utilization during exercise is of utmost importance. The aim of this review is to provide an extensive overview of the current knowledge regarding the pathways involved in the regulation of substrate utilization during exercise. By synthesizing existing research, we can gain a holistic perspective on the intricate relationship between exercise, metabolism, and fuel selection. This advanced understanding has the potential to drive advancements in the field of exercise science and contribute to the development of personalized exercise strategies for individuals looking to optimize their performance and overall health.

Differential effects of heart failure with reduced ejection fraction on locomotor and respiratory muscles

Abstract Background Muscle weakness impairs quality-of-life, exercise capacity, and survival in patients with heart failure and reduced left ventricular ejection fraction (HFrEF). However, the effects on systemic concentrations and local expression of inflammatory cytokines and myokines as well as metabolic markers might differ between locomotor and respiratory muscles. Purpose We prospectively evaluated clinical, functional, and molecular alterations of the diaphragm and the M. vastus lateralis (MVL) from HFrEF patients receiving a left ventricular assist device compared to patients without heart failure undergoing elective coronary bypass grafting (control). Methods Participants (Controls=21, HFrEF=18) underwent cardiopulmonary exercise and respiratory and leg muscle testing. Serum concentrations and local expression of inflammatory cytokines and myokines as well as key enzymes of metabolic pathways were examined in biopsies of the diaphragm and MVL. Results Exercise capacity, respiratory muscle function and endurance force of locomotor muscles were significantly reduced in HFrEF compared with controls (all p<0.05). The serum concentration of Il-6, Il-1beta and TNF-alpha were significantly higher or solely detectable in HFrEF compared with controls. Local mRNA expression of Il-6 was not different in MVL but 2.2-fold higher in the diaphragm of HFrEF compared with controls (p=0.013). In contrast, mRNA expression of Il-6 receptor was significantly reduced by 38% (p=0.004) in MVL of HFrEF compared with controls but comparable in the diaphragm. Serum concentrations of FGF-21 and Musclin were significantly higher in HFrEF compared with controls (all p<0.05). Local mRNA expression of FGF-21 was significantly lower in both MVL and diaphragm of HFrEF compared with controls. FGF-21 receptor 1 mRNA expression was reduced by 18% in the MVL of HFrEF (p=0.02), whereas co-receptor klotho was comparable to controls. In the diaphragm, FGF-21 receptor 1 mRNA expression was comparable between HFrEF and controls, but the co-receptor klotho had a 5-fold higher mRNA expression in HFrEF (p=0.002). We examined the activity of key enzymes of glucose, lipid and ketone metabolism as well as key enzymes of the Krebs cycle. The main differences were found for ß-hydroxyacyl-CoA Dehydrogenase in the diaphragm with a 1.6-fold higher activity in HFrEF compared with controls (p=0.01) and for succinyl-CoA: 3-ketoacid-coenzyme A transferase in the MVL with a 2-fold higher activity in HFrEF compared with controls (p<0.01) indicating a main utilization of lipids in the diaphragm and of ketones in the MVL for energy supply. Conclusions HFrEF induced divergent effects on inflammatory markers, myokine expression and metabolic parameters in locomotor and respiratory muscles in HFrEF patients compared with controls. This indicates that different molecular alterations contribute to locomotor/respiratory muscle dysfunction and reduced whole-body exercise capacity.

Myo-inositol improves osmoregulation by promoting lipid utilization in Nile tilapia (Oreochromis niloticus)

This research explores the influence of myo-inositol (MI) on the hypertonic stress adaptation of Nile tilapia (Oreochromis niloticus) by increasing lipid utilization under long-term salinity stress. A two-factor interactive experiment was used, and diets containing either normal lipids (NL, 7%) or high lipids (HL, 15%) contained three MI concentrations of 0, 400, and 1200 mg/kg in each lipid diet. Fish were fed six diets under 20 psu (practical salinity units [psu]) for eight weeks. Under long-term hypertonic stress, dietary MI supplementation significantly improved the growth performance of O. niloticus (P < 0.05). Dietary 1200 mg/kg MI supplementation significantly promoted protein deposition and reduced fat accumulation in the whole fish (P < 0.05). The HL diet significantly caused lipid accumulation in the liver, while dietary 1200 mg/kg MI addition alleviated lipid accumulation by promoting the expression of genes related to lipolysis (PPAR-α; ATGL and CPT) and inhibiting the expression of genes related to lipid synthesis (SREBP; DGAT and FAS) (P < 0.05). In addition, 400 mg/kg MI significantly reduced serum lipids (TG and LDL-C) (P < 0.05). qPCR showed that the purity of dietary 1200 mg/kg MI significantly upregulated the expression of an ion transporter-related gene (NKA) in gills (P < 0.05). Meanwhile, 400 mg/kg and 1200 mg/kg MI significantly affected the content of fatty acids in the liver and gill (P < 0.05). In addition, dietary 1200 mg/kg MI supplementation significantly increased the antioxidant capacity in the liver of O. niloticus. In conclusion, dietary supplementation with 1200 mg/kg MI could regulate lipid metabolism, promote lipid utilization and improve the osmotic regulation ability of O. niloticus.

Impaired T-Cell Proliferation in Chronic Lymphocytic Leukemia Patients Is Linked to Disturbed Lipid Metabolism and Homeostasis

Background Successful T-cell based anti-cancer therapies require proliferation and longevity of effector T cells, features that highly depend on metabolic processes. T cells from chronic lymphocytic leukemia (CLL) patients are characterized by acquired T-cell dysfunction, resulting in impaired activation, proliferation and cytotoxicity upon in-vitro activation (van Bruggen et al, Blood 2019). Whilst the role of glucose metabolism in activated T-cells is extensively studied, the contribution of other energy sources is less clear. Lipid metabolism has only recently come into focus as an important source of energy for immune cells. Aims Molecular and functional analysis of the lipid metabolic pathway in T cells from CLL patients. Methods Peripheral blood mononuclear cells (PBMCs) of untreated CLL patients and, as controls, age-matched healthy donors (HD) were studied. T cells at baseline and after TCR stimulation were analyzed molecularly using transcriptomics and lipidomics, and extensively characterized at protein level by flow cytometry and confocal imaging. Lipid metabolism was manipulated through culturing cells in lipoprotein deficient serum (LPDS), or in the presence of agonists and inhibitors of specific regulatory pathways. Results We found the uptake of lipids, specifically cholesterol, during T-cell activation essential for proliferation, which was evidenced by a nearly absent proliferative capacity of HD T cells in the lack of exogenous lipids which was fully rescued by re-addition of cholesterol-rich low-density lipoproteins (LDL). As CLL T cells portray an altered proliferation pattern even when cultured in normal medium, transcriptomic analysis was performed to investigate the expression of key lipid metabolism genes. CLL T-cells had reduced expression of the master transcription factors SREBP1/2, governing lipid and cholesterol metabolism, when stimulated in the presence of their autologous CLL cells (Figure 1A). Accordingly, downstream protein involved in the synthesis and desaturation of lipids and LDL uptake (specifically FASN, LDL-R and SCD) were significantly reduced in CLL compared to HD T cells. Remarkably, despite reduced capacity for LDL uptake, an accumulation of neutral lipids was found in CLL T cells especially upon stimulation (Figure 1B), a feature earlier described in dysfunctional macrophages. The lipid accumulation observed in CLL T cells was supported by the lack of expression of ATGL, a crucial enzyme for the utilization of neutral lipids for energy production and building of new membranes. In line with this, mitochondrial lipid oxidation was decreased in stimulated CLL T cells compared to HD. To investigate the composition of the accumulated lipids, lipidomics analysis was performed, revealing differential abundance of specific lipid classes in stimulated CLL versus HD T cells. Triglycerides were increased while cholesterol esters and phospholipids were reduced in CLL T cells. Triglycerides likely constitute the neutral lipids accumulation found in these cells. As cholesterol esters and phospholipids are essential for proper membrane formation, reduced levels of these species can contribute to the reduced proliferative capacity of CLL T cells. Summary/conclusion Altogether, the results presented here demonstrate a disturbed lipid composition and utilization in CLL T-cells, which contributes to T-cell dysfunction on at least two levels: decreased bioenergetics and decreased proliferation. Likewise, lipid deprivation due to both decreased uptake and a misbalanced lipidome leads to altered T-cell function. Therefore, strategies to increase lipid uptake, synthesis and utilization in order to rebalance homeostasis could ameliorate CLL T-cell dysfunction and specifically proliferation-defects in CLL.

No Net-Utilization of Intramuscular Lipid Droplets during Repeated High-Intensity Intermittent Exercise.

Intramuscular lipids are stored as subsarcolemmal or intramyofibrillar droplets with potential diverse roles in energy metabolism. We examined intramuscular lipid utilization through transmission electron microscopy during repeated high-intensity intermittent exercise, an aspect that is hitherto unexplored. Seventeen moderately-to-well-trained males underwent three periods (EX1-EX3) of 10 x 45-s high-intensity cycling (~100-120% watt max) combined with maximal repeated sprints (~250-300% watt max). M. vastus lateralis biopsies were obtained at baseline, after EX1, and EX3. During the complete exercise session, no net decline in neither subsarcolemmal nor intermyofibrillar lipid volume density occurred. However, a temporal relationship emerged for subsarcolemmal lipids with an ~11% increase in droplet size after EX1 (P=0.024), which reverted to baseline levels after EX3 accompanied by a ~30% reduction in the numerical density of subsarcolemmal lipid droplets compared to both baseline (P=0.019) and after EX1 (P=0.018). Baseline distinctions were demonstrated with a ~2-fold higher intermyofibrillar lipid volume in type 1 vs. type 2 fibers (P=0.008), mediated solely by a higher number rather than size of lipid droplets (P<0.001). No fiber type-specific differences were observed in subsarcolemmal lipid volume although type 2 fibers exhibited ~17% larger droplets (P=0.034) but a lower numerical density (main effect; P=0.010) including 3% less droplets at baseline. Collectively, these findings suggest that intramuscular lipids do not serve as an important substrate during high-intensity intermittent exercise, however, the repeated exercise pattern mediated a temporal remodeling of the subsarcolemmal lipid pool. Furthermore, fiber type- and compartment-specific differences were found at baseline underscoring the heterogeneity in lipid droplet deposition.

Eggs of the mosquito Aedes aegypti survive desiccation by rewiring their polyamine and lipid metabolism.

Upon water loss, some organisms pause their life cycles and escape death. While widespread in microbes, this is less common in animals. Aedes mosquitoes are vectors for viral diseases. Aedes eggs can survive dry environments, but molecular and cellular principles enabling egg survival through desiccation remain unknown. In this report, we find that Aedes aegypti eggs, in contrast to Anopheles stephensi, survive desiccation by acquiring desiccation tolerance at a late developmental stage. We uncover unique proteome and metabolic state changes in Aedes embryos during desiccation that reflect reduced central carbon metabolism, rewiring towards polyamine production, and enhanced lipid utilisation for energy and polyamine synthesis. Using inhibitors targeting these processes in blood-fed mosquitoes that lay eggs, we infer a two-step process of desiccation tolerance in Aedes eggs. The metabolic rewiring towards lipid breakdown and dependent polyamine accumulation confers resistance to desiccation. Furthermore, rapid lipid breakdown is required to fuel energetic requirements upon water reentry to enable larval hatching and survival upon rehydration. This study is fundamental to understanding Aedes embryo survival and in controlling the spread of these mosquitoes.

Glycerol monolaurate improves growth, lipid utilization and antioxidative status of white-leg shrimp, Penaeus vannamei fed with varying protein-lipid diets reared in inland saline water

Higher lipid at suboptimum dietary protein level can be a suitable approach to formulate cost-effective feed for cultured fish. However, excess lipid may cause metabolic burden to animals resulted in growth retardation with lipid deposition. Therefore, a feeding trial of 60 days was conducted to assess the effect of glycerol monolaurate (GML) supplemented in varying protein and lipid diets on growth, lipid utilization, antioxidant status and biochemical indices of white-leg shrimp, Penaeus vannamei juveniles reared in inland saline water (ISW). Accordingly, three hetero-lipidic (5–9% lipid), hetero-nitrogenous (30–36% CP), and hetero-energetic (379–400 Kcal DE/100 g) diets with three levels of GML (0%, 0.07% and 0.1%) were formulated for nine diets viz. P36L5G0 (36% CP, 5% lipid and 0% GML), P36L5G0.07 (36% CP, 5% lipid and 0.07% GML), P36L5G0.1 (36% CP, 5% lipid and 0.1% GML), P33L7G0 (33% CP, 7% lipid and 0% GML), P33L7G0.07 (33% CP, 7% lipid and 0.07% GML), P33L7G0.1 (33% CP, 7% lipid and 0.1% GML), P30L9G0 (30% CP, 9% lipid and 0% GML), P30L9G0.07 (30% CP, 9% lipid and 0.07% GML) and P30L9G0.1 (30% CP, 9% lipid and 0.1% GML). Five hundred and forty P. vannamei juveniles (4.02 ± 0.01 g) were randomly distributed following 3 × 3 factorial design. Highest (p < 0.05) weight gain. Specific growth rate, protein efficiency ratio, lipid efficiency ratio, whole body protein with lowest feed conversion ratio, whole body lipid, and hepatopancreas–somatic index was recorded in P33L7G0.1 group. Hepatopancreatic amylase and lipase activities increased (p < 0.05) significantly while protease activity decreased in relation to increased levels of dietary lipid. However, supplementing GML resulted in increased (p < 0.05) activity of all digestive enzymes and highest activity was found in 0.1% GML fed group. Lipid metabolic enzyme glucose-6-phosphate dehydrogenase and carnitine palmitoyltransferase-1 activities were found maximum (p < 0.05) in P33L7G0.1 group and lowest in P36L5G0 group. Hepatopancreatic and branchial superoxide dismutase and catalase activities showed a decreased (p < 0.05) and increased trend with dietary lipid levels, while GML reduced the activities and lowest activity recorded in P33L7G0.1 group. Shrimps of 9% lipid group exhibited highest serum malondialdehyde, glucose, cholesterol and triglyceride levels but 0.1% GML significantly showed the lowest levels that other groups. Higher hemocyanin and total protein observed in 33% dietary protein and 0.1% GML fed group. Therefore, 33% protein, 7% lipid with 0.1% GML is optimum for maximum growth performance, lipid utilization, whole body protein, and antioxidative status of white-leg shrimp, P. vannamei juveniles reared in ISW of 10 ppt.

The Role of the Nuclear Receptor FXR in Arsenic-Induced Glucose Intolerance in Mice.

Inorganic arsenic in drinking water is prioritized as a top environmental contaminant by the World Health Organization, with over 230 million people potentially being exposed. Arsenic toxicity has been well documented and is associated with a plethora of human diseases, including diabetes, as established in numerous animal and epidemiological studies. Our previous study revealed that arsenic exposure leads to the inhibition of nuclear receptors, including LXR/RXR. To this end, FXR is a nuclear receptor central to glucose and lipid metabolism. However, limited studies are available for understanding arsenic exposure-FXR interactions. Herein, we report that FXR knockout mice developed more profound glucose intolerance than wild-type mice upon arsenic exposure, supporting the regulatory role of FXR in arsenic-induced glucose intolerance. We further exposed mice to arsenic and tested if GW4064, a FXR agonist, could improve glucose intolerance and dysregulation of hepatic proteins and serum metabolites. Our data showed arsenic-induced glucose intolerance was remarkably diminished by GW4064, accompanied by a significant ratio of alleviation of dysregulation in hepatic proteins (83%) and annotated serum metabolites (58%). In particular, hepatic proteins "rescued" from arsenic toxicity by GW4064 featured members of glucose and lipid utilization. For instance, the expression of PCK1, a candidate gene for diabetes and obesity that facilitates gluconeogenesis, was repressed under arsenic exposure in the liver, but revived with the GW4064 supplement. Together, our comprehensive dataset indicates FXR plays a key role and may serve as a potential therapeutic for arsenic-induced metabolic disorders.

Hypolipidemic Activity of a Polyherbal Formulation in Triton WR-1339 and High Fat Diet-induced Hyperlipidemic Rats

In hyperlipidemic wistar albino rat models produced by triton and diet, the efficacy of polyherbal formulations containing four different plants was assessed. Rats exposed to Triton WR 1339 had their blood cholesterol and triglyceride levels raised. However, this was reversed when the rats were given syrup or a comparable formulation. Both formulations better lipid outlines in rats with high-fat diet-induced hyperlipidemia. Effects were marginally better with the usual medication Atrovastatin. Liver sinusoidal capillary dilations, cytoplasmic fatty infiltration, and granular degeneration were considerably reduced in polyherbal formulation-treated group II animals related with other groups. As per results, polyherbal formulations in dyslipidaemic circumstances reduce lipid levels by blocking the production of cholesterol and reducing lipid utilization.

Antiglycation, antifibrillation and antioxidative effects of para coumaric acid and vitamin D; an in-vitro and in-silico comparative-cum-synergistic approach

Diabetes Mellitus is a metabolic disorder that results in impaired utilization of carbohydrates, lipids, and proteins. Severe hyperglycemia is its principal clinical symptom. Human serum albumin (HSA) is used as a model protein since it is viewed as a sign of glycaemic management because it is more likely to get glycated in diabetic people than other proteins. Para-coumaric acid (pCA), a phenolic acid, and Vitamin D (vit-D) are used as protective agents. In the present work, we deduce a synergistic-cum-comparative effect of pCA and vit-D, expecting some improvement in the efficacy of pCA when combined with vit-D. Methods employed are DPPH radical scavenging activity, In-vitro glycation of HSA, UV–vis spectroscopy, fluorescence analysis, and circular dichroism measurement. After treatment, increasein the absorbance and fluorescence intensity were reduced along with normalization of CD value. . The glycation-mediated fibrillation assessed by Congo-Red and Thioflavin T (ThT) were found to be diminishedwhen HSA was treated with equimolar concentration of p-CA and vit-D- treatment. Fructosamine adduct formation and lysine modificationwas also decreased, while inhibition to hemolysis and lipid peroxidation was found to increase upon treatment. The reactive oxygen species generation detection was also performed in lymphocytes treated with various protein samples. Docking results further confirmed theblocking some glycation-prone amino acids by both compounds. The study shows that the combination in the ratio of 1:1 has provided higher overall protection comparable to aminoguanidine (AG), the molecule which is utilized as a positive control.

Loss of Ptpmt1 limits mitochondrial utilization of carbohydrates and leads to muscle atrophy and heart failure in tissue-specific knockout mice.

While mitochondria in different tissues have distinct preferences for energy sources, they are flexible in utilizing competing substrates for metabolism according to physiological and nutritional circumstances. However, the regulatory mechanisms and significance of metabolic flexibility are not completely understood. Here, we report that the deletion of Ptpmt1, a mitochondria-based phosphatase, critically alters mitochondrial fuel selection - the utilization of pyruvate, a key mitochondrial substrate derived from glucose (the major simple carbohydrate), is inhibited, whereas the fatty acid utilization is enhanced. Ptpmt1 knockout does not impact the development of the skeletal muscle or heart. However, the metabolic inflexibility ultimately leads to muscular atrophy, heart failure, and sudden death. Mechanistic analyses reveal that the prolonged substrate shift from carbohydrates to lipids causes oxidative stress and mitochondrial destruction, which in turn results in marked accumulation of lipids and profound damage in the knockout muscle cells and cardiomyocytes. Interestingly, Ptpmt1 deletion from the liver or adipose tissue does not generate any local or systemic defects. These findings suggest that Ptpmt1 plays an important role in maintaining mitochondrial flexibility and that their balanced utilization of carbohydrates and lipids is essential for both the skeletal muscle and the heart despite the two tissues having different preferred energy sources.

Loss of Ptpmt1 limits mitochondrial utilization of carbohydrates and leads to muscle atrophy and heart failure in tissue-specific knockout mice

While mitochondria in different tissues have distinct preferences for energy sources, they are flexible in utilizing competing substrates for metabolism according to physiological and nutritional circumstances. However, the regulatory mechanisms and significance of metabolic flexibility are not completely understood. Here, we report that the deletion of Ptpmt1, a mitochondria-based phosphatase, critically alters mitochondrial fuel selection – the utilization of pyruvate, a key mitochondrial substrate derived from glucose (the major simple carbohydrate), is inhibited, whereas the fatty acid utilization is enhanced. Ptpmt1 knockout does not impact the development of the skeletal muscle or heart. However, the metabolic inflexibility ultimately leads to muscular atrophy, heart failure, and sudden death. Mechanistic analyses reveal that the prolonged substrate shift from carbohydrates to lipids causes oxidative stress and mitochondrial destruction, which in turn results in marked accumulation of lipids and profound damage in the knockout muscle cells and cardiomyocytes. Interestingly, Ptpmt1 deletion from the liver or adipose tissue does not generate any local or systemic defects. These findings suggest that Ptpmt1 plays an important role in maintaining mitochondrial flexibility and that their balanced utilization of carbohydrates and lipids is essential for both the skeletal muscle and the heart despite the two tissues having different preferred energy sources.