Muscle Triglyceride Research Articles

A Comparative Study of the Effect of Including Full-Fat Tenebrio molitor for Replacing Conventional Ingredients in Practical Diets for Dicentrarchus labrax Juveniles

Tenebrio molitor (TM) meal is a potential alternative ingredient to plant and fishmeal in aquafeeds due to its high protein content, digestibility, and low environmental impact. However, its low n-3 PUFA (EPA and DHA) content represents one of its main limitations. This study evaluated the effects of replacing fishmeal and plant-derived ingredients (plant proteins and soybean oil) with full-fat TM meal on the growth performance and lipid composition of tissues in juvenile European seabass (Dicentrarchus labrax). Four experimental diets, including 5–10% TM for replacing fishmeal and soybean oil (FM5 and FM10) and 10–20% TM for substituting plant protein ingredients and soybean oil (PI10 and PI20), were tested over 49 days against a control diet (CT). Fish fed on PI20 exhibited the highest growth performance (final weight: 49.73 g and SGR: 1.78% day−1) compared to fish fed on FM (final weight: 47.0 g and SGR: 1.62% day−1) and CT (final weight: 48.45 g and SGR: 1.71% day−1). In general, the diets containing TM modulated the lipid profile in fish tissues by reducing the liver lipid content and muscle triglycerides and increasing the n-3/n-6 ratio compared to the CT diet. However, the most effective approach for modulating those parameters seems to be using the TM meal for replacing the plant ingredients instead of substituting fishmeal. Moreover, this feeding strategy, demonstrated to be useful for promoting the growth of fish owing to the use of the TM meal for replacing fishmeal, resulted in a slight reduction in the final weight of the fish.

Genetic Deletion of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Homeostasis and Impairs Exercise Tolerance.

Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways in which inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is still poorly understood. Since skeletal muscle is a major contributor to energy homeostasis, we have developed a mouse model in which skeletal muscle IPMK is specifically deleted and examined how a loss of IPMK affects whole-body metabolism. Here, we report that mice in which IPMK knockout is deleted, specifically in the skeletal muscle, displayed an increased body weight, disrupted glucose tolerance, and reduced exercise tolerance under the normal diet. Moreover, these changes were associated with an increased accumulation of triglyceride in skeletal muscle. Furthermore, we have confirmed that a loss of IPMK led to reduced beta-oxidation, increased triglyceride accumulation, and impaired insulin response in IPMK-deficient muscle cells. Thus, our results suggest that IPMK mediates the whole-body metabolism via regulating muscle metabolism and may be potentially targeted for the treatment of metabolic syndromes.

Sulforaphane enhanced muscle growth by promoting lipid oxidation through modulating key signaling pathways.

Sulforaphane (SFN) has shown diverse effects on human health and diseases. SFN was administered daily to C57BL/6J mice at doses of 1 mg/kg (SFN1) and 3 mg/kg (SFN3) for 8 weeks. Both doses of SFN accelerated body weight increment. The cross-sectional area and diameter of Longissimus dorsi (LD) muscle fibers were enlarged in SFN3 group. Triglyceride (TG) and total cholesterol (TC) levels in LD muscle were decreased in SFN groups. RNA sequencing results revealed that 2455 and 2318 differentially expressed genes (DEGs) were found in SFN1 and SFN3 groups, respectively. Based on GO enrichment analysis, 754 and 911 enriched GO terms in the SFN1 and SFN3 groups, respectively. KEGG enrichment analysis shown that one KEGG pathway was enriched in the SFN1 group, while six KEGG pathways were enriched in the SFN3 group. The expressions of nine selected DEGs validated with qRT-PCR were in line with the RNA sequencing data. Furthermore, SFN treatment influenced lipid and protein metabolism related pathways including AMPK signaling, fatty acid metabolism signaling, cholesterol metabolism signalling, PPAR signaling, peroxisome signaling, TGFβ signaling, and mTOR signaling. In summary, SFN elevated muscle fibers size and reduced TG and TC content of in LD muscle by modulating protein and lipid metabolism-related signaling pathways.

Genistein in combination with Chlorogenic acid ameliorates insulin resistance and oxidative stress in skeletal muscle of high-fat diet fed mice

Objectives: Increasing evidence has demonstrated that oxidative stress plays a significant role in the pathogenesis of muscle insulin resistance. The beneficial impacts of genistein (GEN) and chlorogenic acid (CGA) on insulin resistance have already been revealed. However, their combined effects on skeletal muscle oxidative stress and insulin resistance have not been completely understood. The aim of the present study was to determine the effect of GEN in combination with CGA on skeletal muscle insulin resistance in high-fat diet (HFD) fed C57BL/6 mice.
 Methods: C57BL/6 male mice were fed an HFD for 15 weeks. The mice were then divided into five groups: standard chow diet (SCD), HFD, HFD + GEN, HFD + CGA, and HFD + GEN + CGA for 10 weeks.
 Results: The findings indicated that single treatment with GEN or CGA, and with a stronger effect of GEN+CGA combined treatment, decreased body weight gain and improved glucose intolerance. Moreover, following treatment with GEN and CGA alone or in combination with further effect, the level of plasma and muscle triglyceride (TG) were reduced. Furthermore, the combination therapy of GEN and CGA with greater efficacy than the single treatments, could decrease several oxidative stress markers in the skeletal muscle. Treatment with GEN and CGA alone or in combination could increase the expression of NF-E2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P): Quinone Oxidoreductase 1 (NQO1).
 Conclusion: The data of this study suggest that the combination of GEN and CGA might ameliorate insulin resistance and reduce oxidative stress in the skeletal muscle of mice fed HFD.

Astaxanthin Ameliorates Worsened Muscle Dysfunction of MDX Mice Fed with a High-Fat Diet through Reducing Lipotoxicity and Regulating Gut Microbiota.

Duchenne muscular dystrophy (DMD), a severe X-linked inherited neuromuscular disease, has a high prevalence of obesity. Obesity exacerbates muscle damage and results in adverse clinical outcomes. Preventing obesity helps DMD patients delay disease progression and improve quality of life. Astaxanthin (AX) is a kind of carotenoid which has antioxidant and anti-adipogenesis effects. In this study, male C57BL/10ScSnDmdmdx/J mice were fed with a normal diet, a high-fat diet (HFD), and an HFD containing AX for 16 weeks, respectively. The results showed that AX significantly increased gastrocnemius fiber cross-section area and grip strength, improved treadmill endurance test and mitochondrial morphology, and reduced muscle triglyceride and malonaldehyde levels compared to the HFD. Lipidomic analysis revealed that AX decreased high levels of triglyceride, diglyceride, ceramides, and wax ester induced by HFD. Gut microbiota analysis indicated that AX supplementation failed to alleviate abnormal microbiota diversity, but increased the relative abundances of Akkermansia, Bifidobacterium, Butyricicoccus, and Staphylococcus. In conclusion, AX was expected to alleviate disease progression associated with obesity in DMD patients by reducing lipotoxicity and increasing the abundance of beneficial bacteria.

Combination therapy of metformin and morin attenuates insulin resistance, inflammation, and oxidative stress in skeletal muscle of high-fat diet-fed mice.

Lipid accumulation, inflammation, and oxidative stress are the most important causes of muscle insulin resistance. The aim of this study was to investigate the single and combined treatment effects of metformin (MET) and morin (MOR) on lipid accumulation, inflammation, and oxidative stress in the skeletal muscle of mice fed a high-fat diet. The mice were supplemented with MET (230 mg/kg diet), MOR (100 mg/kg diet), and MET + MOR for 9 weeks. Our results revealed that single treatment with MET or MOR, and with a stronger effect of MET + MOR combined treatment, reduced body weight gain, improved glucose intolerance and enhanced Akt phosphorylation in the muscle tissue. In addition, plasma and muscle triglyceride levels were decreased after treatment with MET and MOR. The expression of genes involved in macrophage infiltration and polarization and pro-inflammatory cytokines showed that MET + MOR combined treatment, significantly reduced inflammation in the muscle. Furthermore, combined treatment of MET + MOR with greater efficacy than the single treatment improved several oxidative stress markers in the muscle. Importantly, combined treatment of MET and MOR could increase the expression of nuclear factor erythroid 2-related factor 2, the master regulator of the antioxidant response. These findings suggest that combination of MET with MOR might ameliorate insulin resistance, inflammation, and oxidative stress in the skeletal muscle of mice fed high-fat diet.

Antidiabetic properties of Tarchonanthus camphoratus in fructose-induced diabetic Wistar rats

Tarchonantus camphoratus (TC) has been used traditionally to manage diabetes mellitus (DM) in Kenya but its efficacy has not been scientifically evaluated. This study aimed at evaluating the antidiabetic properties of TC crude leaf extract in diet-induced diabetic Wistar rats. DM was induced using high fructose (25% w/v) in drinking water for 12 weeks. Rats were divided into five groups (n=7): Groups I: normal control; II; diabetic untreated; III, IV & V; diabetic treated (21 days) with metformin (100 mg/kg.bw/day), 300 and 600 mg/kg.bw/day of TC extract respectively. Fasting body weights and blood glucose levels were monitored weekly. Oral glucose tolerance test, serum lipid profile, creatinine, urea, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total proteins (TP), C-reactive protein (CRP), albumin (ALB) and triglyceride (TG) mass in skeletal muscle were analysed at end of the study. Qualitative phytochemical analysis was done using standard procedures. Diabetic untreated rats had significantly higher body weights (p ˂0.05) compared to other groups. There was a significant reduction in fasting blood glucose in TC treatment groups compared to untreated controls. Increased glucose tolerance was observed in treated groups. TC extract significantly improved fructose-induced hypertriglyceridemia compared to DM groups. ALP, ALT, and CRP were significantly lowered while TP and ALB were elevated in the extract treated rats compared with untreated DM rats. DM group also exhibited significantly higher skeletal muscle TG mass when compared to normal control and diabetic treated groups. The phytochemical-rich TC leaf extract therefore possess potential alternative medicine for DM management.

Garcinia cambogia Extract Increased Hepatic Levels of Lipolysis-Stimulated Lipoprotein Receptor and Lipids in Mice on Normal Diet.

Garcinia cambogia extract (GCE) is a popular weight-loss supplement that also lowers plasma triglyceride (TG) levels. We hypothesized that GCE-mediated inhibition of ATP citrate lyase and thereby hepatic TG production could lead to compensatory mechanisms, including increased hepatic TG uptake via lipoprotein receptors. GCE (20 mg/day) administered 40 days orally to female C57BL/6Rj mice on a standard chow diet led to a decrease in both plasma fasting and post-prandial TG-rich lipoprotein levels, but with no significant change in body weight gain. Lipolysis stimulated lipoprotein receptor (LSR) protein levels, but not those of LDL-receptor, were increased as compared to controls. Mouse Hepa1-6 cells treated with the GCE active ingredient, hydroxycitrate, also led to increased LSR protein levels. Hepatic total cholesterol, TG, and muscle TG contents were higher in GCE-treated animals as compared to controls, whereas adipose TG levels were unchanged. LSR and LDL-receptor protein levels were correlated with liver total cholesterol, but only LDL-receptor was associated with liver TG. These results show that GCE treatment in mice on a standard chow diet led to significantly increased liver and muscle lipids, with no significant change in adipose tissue TG levels, which should be considered in the long-term use of GCE.

Dietary L-theanine supplementation improves antioxidant capacity and lipid metabolism in finishing pigs

The objective of this study was to investigate the effects of dietary L-theanine (LTH) supplementation on finishing pigs' antioxidant capacity and lipid metabolism. Results showed that dietary LTH supplementation increased the activity of antioxidant enzymes and decreased the content of malondialdehyde in serum, longissimus dorsi muscle (LD muscle), and liver of finishing pigs (P < 0.05). Dietary LTH supplementation decreased serum low-density lipoprotein cholesterol content and increased high-density lipoprotein cholesterol content (P < 0.05). Moreover, LTH-containing diet decreased the contents of triglyceride and total cholesterol in serum, LD muscle, and liver (P < 0.05). In liver and LD muscle, LTH activated Nrf2-Keap1 signaling pathway, increased mRNA expression levels of genes related to lipolysis and fatty acid oxidation and reduced the expression levels of genes related to adipogenesis (P < 0.05). According to our study, nutritional supplementation with LTH enhanced finishing pigs' antioxidant capacity and lipid metabolism.

A Combination of Soy Isoflavone and L-Carnitine Improves Running Endurance in Mice.

The present study aimed to investigate the effect of APIC, a mixture containing soy isoflavone and L-carnitine on running endurance. Male C57BL/6 mice were orally administered APIC for 8 weeks. The APIC group exhibited a significant increase in treadmill running time until exhaustion compared to the control group. The respiratory exchange ratio in the APIC group was lower, indicating an enhancement in fatty acid oxidative metabolism. Furthermore, APIC supplementation increased the proportion of oxidative myofibers. Biochemical parameters associated with endurance capacity were also affected by APIC, as evidenced by increased muscle ATP levels and decreased levels of muscle triglycerides and blood lactate. qPCR and immunoblot analysis of C2C12 myotubes and gastrocnemius muscles indicated that APIC treatment stimulated AMPK signaling, mitochondrial biogenesis, and fatty acid metabolism. Additionally, treatment with APIC led to an increased oxygen consumption rate in C2C12 myotubes. Collectively, these findings suggest that APIC supplementation enhances mitochondrial biogenesis, promotes a switch from glycolytic to oxidative fiber types, and improves fatty acid metabolism through the activation of the AMPK signaling pathway in murine skeletal muscle. Ultimately, these effects contribute to the enhancement of running endurance.

Effects of vegetable oil replacement on intramuscular fat deposition and flesh quality of large yellow croaker (Larimichthys crocea) juveniles

The present study was conducted to investigate the effects of vegetable oil replacement on intramuscular fat deposition and flesh quality of large yellow croaker (Larimichthys crocea) juveniles. Five experiment diets were formulated with different vegetable oils substituting fish oil (fish oil group: FO, soybean oil group: SO, linseed oil group: LO, palm oil group: PO and olive oil group: OO). Juvenile large yellow croaker with an initial size of 6.04 ± 0.08 g were selected and randomly assigned to seawater cages (4 m × 4 m × 4 m). Each diet treatment was set up for three replicates, and 60 juvenile large yellow croaker were cultured in each replicate to carry out the experiment. The formal experiment lasted for 10 weeks, and the cultured fish was hand fed to apparent satiation twice daily at 6:00 am and 5:00 pm. During the experiment, the water temperature ranged from 19.3 °C to 22.8 °C, the salinity ranged from 25.6 to 29.9‰, and the dissolved oxygen level ranged from 6.3 to 7.4 mg/L. Results showed that compared with the FO group, the muscle triglyceride in SO, LO and PO group was significantly decreased (P < 0.05), which led to the significant up-regulations of muscle hardness, chewiness and gumminess (P < 0.05). SO, LO and PO treatments significantly up-regulated the gene expression of pparα and cpt1b compared with FO treatment (P < 0.05). Meanwhile, SO, LO and PO groups also enhanced the activity of muscle citrate synthase. Additionally, gene expression of pgc1-α, nrf1 and tfam was significantly up-regulated in the SO group compared with the FO group. The results of the muscle transcriptome indicated that compared with the FO group, the SO group could significantly increase the gene expression of prkag2 and the protein expression of p-AMPK/AMPK (P < 0.05). In conclusion, replacing fish oil with different vegetable oils could affect muscle sensory quality indices of juvenile large yellow croaker by changing intramuscular fat deposition, which might be due to the regulation on muscle mitochondrial biogenesis and fatty acid β-oxidation.

Progesterone Has No Impact on the Beneficial Effects of Estradiol Treatment in High-Fat-Fed Ovariectomized Mice

In recent decades, clinical and experimental studies have revealed that estradiol contributes enormously to glycemic homeostasis. However, the same consensus does not exist in women during menopause who undergo replacement with progesterone or conjugated estradiol and progesterone. Since most hormone replacement treatments in menopausal women are performed with estradiol (E2) and progesterone (P4) combined, this work aimed to investigate the effects of progesterone on energy metabolism and insulin resistance in an experimental model of menopause (ovariectomized female mice-OVX mice) fed a high-fat diet (HFD). OVX mice were treated with E2 or P4 (or both combined). OVX mice treated with E2 alone or combined with P4 displayed reduced body weight after six weeks of HFD feeding compared to OVX mice and OVX mice treated with P4 alone. These data were associated with improved glucose tolerance and insulin sensitivity in OVX mice treated with E2 (alone or combined with P4) compared to OVX and P4-treated mice. Additionally, E2 treatment (alone or combined with P4) reduced both hepatic and muscle triglyceride content compared with OVX control mice and OVX + P4 mice. There were no differences between groups regarding hepatic enzymes in plasma and inflammatory markers. Therefore, our results revealed that progesterone replacement alone does not seem to influence glucose homeostasis and ectopic lipid accumulation in OVX mice. These results will help expand knowledge about hormone replacement in postmenopausal women associated with metabolic syndrome and non-alcoholic fatty liver disease.

Preliminary experience of cardiac proton spectroscopy at 0.75 T.

Recent work on high-performance lower-field MR systems has renewed the interest in assessing relative advantages and disadvantages of magnetic fields less than 1 T. The objective of the present work was to investigate signal-to-noise ratio (SNR) scaling of point-resolved spectroscopy as a function of field strength and to test the feasibility of proton MRS of triglycerides (TGs) in human in vivo myocardium at 0.75 T relative to 1.5 T and 3 T. Measurements at 0.75 T were obtained by temporarily ramping down a clinical 3 T MR scanner. System configurations at 0.75, 1.5 and 3 T featured identical hard- and software, except for differences in transmit/receive coil geometries and receive channel count, which were accounted for in SNR comparisons. Proton MRS was performed at 0.75 T, 1.5 T and 3 T in ex vivo tissue and in vivo calf muscle to measure T1 and T2 values as a function of field strength, which in turn served as input to simulations of SNR scaling and field-dependent TG fit errors. Preliminary in vivo spectra of myocardium were acquired at 0.75 T, 1.5 T and 3 T in healthy subjects. Measurements of both ex vivo tissue and in vivo muscle tissue at 0.75 T versus 1.5 T and 3 T confirmed decreasing T1 and increasing T2 * for decreasing field strengths. Using measured T1 , T2 and T2 * as input and using field-dependent echo time and bandwidth scaling, simulated Cramér-Rao lower bounds of TG amplitudes at 0.75 T were 2.3 and 4.5 times larger with respect to 1.5 T and 3 T, respectively. In vivo measurements demonstrate that human proton spectroscopy of TGs in cardiac muscle is feasible at 0.75 T, supporting the potential practical value of lower-field high-performance MR systems.

Lactobacillus rhamnosus GG administration partially prevents diet-induced insulin resistance in rats: a comparison with its heat-inactivated parabiotic.

Insulin resistance and type 2 diabetes are obesity-related health alterations, featuring an ever-increasing prevalence. Besides inadequate feeding patterns, gut microbiota alterations stand out as potential contributors to these metabolic disturbances. The aim of this study was to investigate whether the administration of a probiotic (Lactobacillus rhamnosus GG) effectively prevents diet-induced insulin resistance in rats and to compare these potential effects with those exerted by its heat-inactivated parabiotic. For this purpose, 34 male Wistar rats were fed a standard or a high-fat high-fructose diet, alone or supplemented with viable or heat-inactivated Lactobacillus rhamnosus GG. The body and white adipose tissue weight increases, induced by the obesogenic diet, were prevented by probiotic and parabiotic administration. The trend towards higher basal glucose levels and significantly higher serum insulin concentration observed in the non-treated animals fed with the obesogenic diet were effectively reverted by both treatments. Similar results were also found for serum adiponectin and leptin, whose levels were brought back by the probiotic and parabiotic administration to values similar to those of the control animals. Noteworthily, parabiotic administration significantly reduced skeletal muscle triglyceride content and activated CPT-1b compared to the non-treated animals. Finally, both treatments enhanced Akt and AS160 phosphorylation in the skeletal muscle compared to the non-treated animals; however, only parabiotic administration increased GLUT-4 protein expression in this tissue. These results suggest that heat-inactivated Lactobacillus rhamnosus GG seem to be more effective than its probiotic of origin in preventing high-fat high-fructose diet-induced insulin resistance in rats.

Dietary supplementation with protein hydrolysates from the shell of red swamp crayfish (Procambarus clarkii) affects growth, muscle antioxidant capacity and circadian clock genes expression of zebrafish (Danio rerio)

Protein hydrolysates are rich in amino acids and bioactive peptides, beneficial for the organism health. This study analyzed not only the effects of dietary supplementation with P. clarkii shell protein hydrolysates (PCSPHs) on the growth performance, muscle biochemical indices and histological characteristics of zebrafish, but also the changes of muscle antioxidant capacity and circadian clock genes expression were also evaluated. After feeding, the final body weight, weight gain rate and specific growth rate of zebrafish fed with PCSPHs supplementation were significantly higher than normal diet, and reduced contents of muscle triglyceride and aspartate aminotransferase. Meanwhile, dietary supplementation with PCSPHs improved total amino acid contents and myofiber structure of zebrafish. Antioxidant enzyme activities of total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) content, and the expression of antioxidant related genes increased with PCSPHs supplementation. Furthermore, the expression of Nrf2 protein showed a significantly up-regulated trend with the increasing of dietary PCSPHs levels. However, it was interesting that the expression of circadian rhythm related genes was also affected by dietary PCSPHs levels, and showed a significant up-regulated and down-regulated trend. The above results showed that dietary supplementation with PCSPHs could promote the growth performance, muscle amino acid contents and myofiber structure of zebrafish, but also enhance the muscle antioxidant capacity and regulates the expression of circadian clock genes. It is hypothesized that this may be related to the expression of antioxidant signaling pathway Nrf2/Keap1. Our study will provide a theoretical basis for improving the muscle quality and health of aquatic animals.

The Effects of Exercise Training on Glucose Homeostasis and Muscle Metabolism in Type 1 Diabetic Female Mice.

Although exercise training is an important recommendation for the management of type 1 diabetes (T1D), most of the available research studies predominantly focus on male subjects. Given the importance of sex as a biological variable, additional studies are required to improve the knowledge gap regarding sex differences in T1D research. Therefore, the purpose of this study was to examine the role of exercise training in mediating changes in glucose homeostasis and skeletal muscle metabolism in T1D female mice. Female mice were injected with streptozotocin (STZ) to induce T1D. Two weeks after STZ injection, control (CON) and STZ mice were exercise trained on a treadmill for 4 weeks. Aerobic exercise training failed to improve glucose tolerance, prevent the decrease in body weight and adipose tissue mass, or attenuate muscle atrophy in T1D female mice. However, insulin sensitivity was improved in T1D female mice after exercise training. Aerobic exercise training maintained skeletal muscle triglyceride content but did not prevent depletion of skeletal muscle or liver glycogen in T1D mice. Gene expression analysis suggested that T1D resulted in decreased glucose transport, decreased ketone body oxidation, and increased fatty acid metabolism in the skeletal muscle, which was not altered by exercise training. These data demonstrate that 4 weeks of aerobic exercise training of a moderate intensity is insufficient to counteract the negative effects of T1D in female mice, but does lead to an improvement in insulin sensitivity.

Dietary L-carnitine supplementation affects flesh quality through modifying the nutritional value and myofibers morphological characteristics in largemouth bass (Micropterus salmoides)

The increase of dietary fat content is becoming prevalent in aquaculture practices, however, the increased dietary fat content is associated with undesirable impacts such as growth inhibition, increased feed conversion ratio, and deteriorated flesh quality. L-carnitine has been used as a feed additive to alleviate severe fat accumulation-induced metabolic disorders, however, its effects on flesh quality remain largely unexplored. In the present study, the effects of L-carnitine on flesh quality were examined by feeding triplicate groups of largemouth bass juveniles (10.75 ± 0.1 g) with three experimental diets including a control diet (CD), a high-fat low-protein diet (HFLPD), and HFLPD supplemented with 0.5 g kg− 1 of L-carnitine for 8 weeks. The results showed that L-carnitine supplementation does not significantly influence final body weight, body length, specific growth rate and carcass ratio. Whole body lipid and muscle triglycerides (TG) contents significantly increased in fish fed the HFLPD compared to the CD group, and L-carnitine supplementation decreased their values. In addition, expression of lipid catabolism related genes such as CPT and ACOX3 were significantly upregulated by L-carnitine application. The fish fed L-carnitine containing diet exhibited markedly higher monounsaturated fatty acids (MUFA) and eicosapentaenoic acid (EPA) contents, and lower saturated fatty acids (SFA) content than the HFLPD-fed fish. Moreover, the texture qualities such as hardness, gumminess and chewiness remarkably decreased in the HFLPD + Car group compared to the HFLPD group. Most specifically, the percentage of medium-diameter fibers (60–120 µm diameter) was significantly decreased in the HFLPD group compared to the CD group, while this was notably reversed by L-carnitine addition. In summary, the present study demonstrated that dietary L-carnitine supplementation enhances nutritional value, alleviates HFLPD-induced metabolic disorders and flesh quality changes in largemouth bass.

555-P: Premenopausal vs. Postmenopausal Women: Effect of Time-Restricted Eating on Body Weight and Metabolic Health Markers

Background: Time restricted eating (TRE) involves restricting the ad libitum eating window to a specific number of hours daily, while water fasting for the remaining hours. Objective: This study examined if changes in body weight and metabolic risk factors during TRE, differ in women based on menopausal status. Methods: This is a secondary analysis of an 8-week TRE study (4-6 h eating window, 18-20 h fasting window daily) conducted in adults with obesity. Male participants were excluded, and female subjects were classified in two groups based on menstrual status: premenopausal (n = 13) , or postmenopausal (n = 19) . Perimenopausal women were excluded from the original study. Results: Body weight decreased in both premenopausal women (-3.3 ± 0.4%) and postmenopausal women (-3.3 ± 0.5%) (main effect of time, P &amp;lt; 0.001) , with no difference between groups (no group × time interaction) by week 8. Adherence in both groups was very high, with premenopausal women adhering to their prescribed eating window on 6.2 ± 0.1 d/week, and postmenopausal women adhering to their window on 6.2 ± 0.2 d/week. Fat mass, lean mass, fasting insulin, insulin resistance, and 8-isoprostane (marker of oxidative stress) were reduced similarly in both groups (main effect of time, P &amp;lt; 0.for all comparisons) . Visceral fat mass, relative skeletal muscle index (RSMI) , blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, fasting glucose, HbA1c, TNF-alpha and IL-6 remained unchanged by 8 weeks in both groups. Conclusion: These findings suggest that the weight loss and metabolic benefits of TRE do not differ between premenopausal and postmenopausal women with obesity. Disclosure K.Gabel: None. K.Varady: None. S.Cienfuegos: None. M.Ezpeleta: None. Funding R01DK119783

Effects of Sustained Hyperglycemia on Skeletal Muscle Lipids in Healthy Subjects.

Sustained increases in plasma glucose promote skeletal muscle insulin resistance independent from obesity and dyslipidemia (ie, glucotoxicity). Skeletal muscle lipids are key molecular determinants of insulin action, yet their involvement in the development of glucotoxicity is unclear. To explore the impact of mild physiologic hyperglycemia on skeletal muscle lipids. Single group pretest-posttest. Healthy males and females with normal glucose tolerance. 72-hour glucose infusion raising plasma glucose by ~50 mg/dL. Skeletal muscle lipids, insulin sensitivity, lipid oxidation. Despite impairing insulin-mediated glucose disposal and suppressing fasting lipid oxidation, hyperglycemia did not alter either the content or composition of skeletal muscle triglycerides, diacylglycerides, or phospholipids. Skeletal muscle ceramides decreased after glucose infusion, likely in response to a reduction in free fatty acid concentrations. Our results demonstrate that the major lipid pools in skeletal muscle are unperturbed by sustained increases in glucose availability and suggest that glucotoxicity and lipotoxicity drive insulin resistance through distinct mechanistic pathways.

Impact of Branched Chain Amino Acid Supplementation on Muscle Lipid Accumulation and Mitochondrial Metabolism

Cross talk between branched‐chain amino acids (BCAAs; valine, leucine and isoleucine), mitochondrial metabolism and lipid accumulation have been shown to occur in several tissues, including skeletal muscle. In fact, defects in BCAA metabolism and their degradation networks coexist with defects in lipid metabolism in insulin resistant muscle. Here, we hypothesized that the relationship between BCAAs and lipid metabolism is due to the ability of BCAAs to modulate mitochondrial oxidative metabolism and lipid accumulation in the muscle. Mice (C57BL/6N) were randomly assigned to a low‐fat diet (LFD; 10% fat kcal), LFD supplemented with BCAAs (LFBA; 150% BCAA), high‐fat diet (HFD; 60% fat kcal) or HFD supplemented with BCAAs (HFBA; 150% BCAA) for 12 or 26 weeks (n = 8‐11 per group). Following the dietary treatments, leg muscle tissue were collected and flash frozen in liquid nitrogen, under feeding and overnight fasting conditions. Lipid accumulation was evaluated by analyzing muscle triglycerides, Oil‐Red‐O staining, and gene expression profiles. Mitochondrial metabolism and BCAA degradation were evaluated using a combination of gas‐chromatography/mass‐spectroscopy based targeted metabolomics and western blot analysis. Levels of BCAAs in the muscle showed significant correlations to their corresponding keto‐acids (p ≤ 0.01). However, supplementation of BCAAs did not affect the levels of mitochondrial tricarboxylic acid (TCA) cycle intermediates or amino acids in the muscle. Further, mitochondrial proteins involved in oxidative phosphorylation also remained similar between non‐supplemented and BCAA supplemented muscle. Muscle tissue from HFD mice had higher lipid accumulation (mg/g ± SEM) (LFD; 8.22 ± 0.91, HFD; 11.03 ± 1.08; p ≤ 0.05), compared to their LFD counterparts. Interestingly, BCAA supplementation for 12‐weeks along with the HFD blunted muscle lipid accumulation (LFBA; 8.62 ± 1.12, HFBA; 9.76 ± 0.75), which was also evidenced from Oil Red‐O staining of the muscle (p = 0.07). A similar lowering of lipid accumulation (p ≤ 0.05) was evident between the HFD vs. HFBA groups, following 26‐weeks on the diets, as quantified by Oil Red‐O staining. Further, the expression of genes involved in lipid accumulation/synthesis Srebp1c (p ≤ 0.05) and Acc1 (p ≤ 0.1) were lower in the 12‐week LFBA vs. their LF counterparts, under fed conditions. Taken together, our results show that BCAAs have the ability to blunt muscle lipid accumulation without altering mitochondrial oxidative metabolism in the muscle.