Lipid Metabolism In Adipose Tissue Research Articles

Legumain-deficient macrophages regulate inflammation and lipid metabolism in adipose tissues to protect against diet-induced obesity

Adipose tissue macrophages (ATMs) are key players in the development of obesity and associated metabolic inflammation, which contributes to systemic metabolic dysfunction, and understanding the interaction between macrophages and adipocytes is crucial for developing novel macrophage-based strategies against obesity. Here, we found that Legumain (Lgmn), a well-known lysosomal cysteine protease, is expressed mainly in the ATMs of obese mice. To further define the potential role of Lgmn-expressing macrophages in the generation of an aberrant metabolic state, LgmnF/F; LysMCre mice, which do not express Lgmn in macrophages, were maintained on a high-fat diet (HFD), and metabolic parameters were assessed. Macrophage-specific Lgmn deficiency protects mice against HFD-induced obesity, diminishes the quantity of proinflammatory macrophages in obese adipose tissues, and alleviates hepatic steatosis and insulin resistance. By analysing the transcriptome and proteome of murine visceral white adipose tissue (vWAT) after HFD feeding, we determined that macrophage Lgmn deficiency causes changes in lipid metabolism and the inflammatory response. Furthermore, the reciprocity of macrophage-derived Lgmn with integrin α5β1 in adipocytes was tested via colocalization analyses. It is further demonstrated in macrophage and adipocyte coculture system that macrophage derived Lgmn bound to integrin α5β1 in adipocytes, therefore attenuating PKA activation, downregulating lipolysis-related proteins and eventually exacerbating obesity development. Overall, our study identified Lgmn as a previously unrecognized regulator involved in the interaction between ATMs and adipocytes contributing to diet-induced obesity and suggested that Lgmn is a potential target for treating metabolic disorders.

Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue

Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormone-sensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.

Effects of aerobic exercise on the regulation of mitochondrial carrier homolog-2 and its influence on the catabolic and anabolic activity of lipids in the mesenteric adipose tissue of obese mice

The aim was to understand the direct impact of aerobic short-term exercise on lipid metabolism, specifically in regulating the mitochondrial carrier homolog 2 (MTCH2) and how it interferes with lipid metabolism in mesenteric adipose tissue. Swiss mice were divided into three groups: control, sedentary obese, and exercised obese. The obese groups were induced into obesity for fourteen weeks of a high-fat diet, and the trained submitted to seven aerobic exercise sessions. The exercise proved the significant increase of the pPerilipin-1, a hormone-sensitive lipase gene, and modulates lipid metabolism by increasing the expression of Mtch2 and acetyl Co-A carboxylase, perhaps occurring as feedback to regulate lipid metabolism in adipose tissue. In conclusion, we demonstrate, for the first time, how aerobic physical exercise increases Mtch2 transcription in mesenteric adipose tissue. This increase was due to changes in energy demand caused by exercise, confirmed by observing the significant reduction in mesenteric adipose tissue mass in the exercised group. Also, we showed that physical exercise increased the phosphorylative capacity of PLIN1, a protein responsible for the degradation of fatty acids in the lipid droplet, providing acyl and glycerol for cellular metabolism. Although our findings demonstrate evidence of MTCH2 as a protein that regulates lipid homeostasis, scant knowledge exists concerning the signaling of the MTCH2 pathway in regulatingfatty acid metabolism. Therefore, unveiling the means of molecular signaling of MTCH2 demonstrates excellent potential for treating obesity.

Anti-Obesity Effect of Jeju Roasted Citrus Peel Extract in High-Fat Diet-Induced Obese Mice and 3T3-L1 Adipocytes Via Lipid Metabolism Regulation.

Lipid accumulation in adipocytes occurs through multifactorial effects such as overnutrition due to unbalanced eating habits, reduced physical activity, and genetic factors. In addition, obesity can be intensified by the dis-regulation of various metabolic systems such as differentiation, lipogenesis, lipolysis, and energy metabolism of adipocytes. In this study, the Jeju roasted peel extract from Citrus unshiu S.Markov. (JRC), which is discarded as opposed to the pulp of C. unshiu S.Markov., is commonly consumed to ameliorate obesity. To investigate the anti-obesity effect of JRC, these studies were conducted on differentiated 3T3-L1 cells and in high-fat diet-induced mice, and related methods were used to confirm whether it decreased lipid accumulation in adipocytes. The mechanism of inhibiting obesity by JRC was confirmed through mRNA expression studies. JRC suppressed lipid accumulation in adipocytes and adipose tissue, and significantly improved enzymes such as alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase and serum lipid profiles. In addition, it effectively modulated the expression of genes related to lipid and energy metabolism in adipose tissue. As a result, these findings suggest that JRC could be a therapeutic regulator of body fat accumulation by significantly alleviating the dis-regulation of intracellular lipid metabolism in adipocytes and by enhancement of energy metabolism (Approval No. CNU IACUC-YB-2023-98).

Inflammation-mediated metabolic regulation in adipose tissue.

Chronic inflammation of adipose tissue is a prominent characteristic of many metabolic diseases. Lipid metabolism in adipose tissue is consistentlydysregulated during inflammation, which is characterized by substantial infiltration by proinflammatory cells and high cytokine concentrations. Adipose tissue inflammation is caused by a variety of endogenous factors, such as mitochondrial dysfunction, reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, cellular senescence, ceramides biosynthesis and mediators of lipopolysaccharides (LPS) signaling. Additionally, the gut microbiota also plays a crucial role in regulating adipose tissue inflammation. Essentially, adipose tissue inflammation arises from an imbalance in adipocyte metabolism and the regulation of immune cells. Specific inflammatory signals, including nuclear factor-κB (NF-κB) signaling, inflammasome signaling and inflammation-mediated autophagy, have been shown to be involved in the metabolic regulation. The pathogenesis of metabolic diseases characterized by chronic inflammation (obesity, insulin resistance, atherosclerosis and nonalcoholic fatty liver disease [NAFLD]) and recent research regarding potential therapeutic targets for these conditions are also discussed in this review.

Cadmium exposure causes transcriptomic dysregulation in adipose tissue and associated shifts in serum metabolites

Cadmium (Cd) is a toxic heavy metal found in natural and industrial environments. Exposure to Cd can lead to various metabolic disturbances, notably disrupting glucose and lipid homeostasis. Despite this recognition, the direct impact of Cd exposure on lipid metabolism within adipose tissue, and the mechanisms underlying these effects, have not been fully elucidated. In this study, we found that Cd accumulates in adipose tissues of mice subjected to Cd exposure. Intriguingly, Cd exposure in itself did not induce significant alterations in the adipose tissue under normal conditions. However, when subjected to cold stimulation, several notable changes were observed in the mice exposed to Cd, including a reduction in the drop of body temperature, a decrease in the size of inguinal white adipose tissue (WAT), and an increase in the expression of thermogenic genes UCP1 and PRDM16. These results indicate that Cd exposure might enhance the responsiveness of adipose tissue to external stimuli and increase the energy expenditure of the tissue. RNA-seq analysis further revealed that Cd exposure altered gene expression profiles, particularly affecting peroxisome proliferator-activated receptor (PPAR)-mediated metabolic pathways, promoting metabolic remodeling in adipose tissue and resulting in the depletion of lipids stored in adipose tissue for energy. Non-targeted metabolomic analysis of mouse serum showed that Cd exposure significantly disrupted metabolites and significantly increased serum fatty acid and triglyceride levels. Correspondingly, population-level data confirmed an association between Cd exposure and elevated levels of serum total cholesterol, total triglycerides, and low-density lipoprotein cholesterol. In summary, we provide substantial evidence of the molecular events induced by Cd that are relevant to the regulation of lipid metabolism in adipose tissue. Our findings suggest that the toxic effects of Cd can impact adipocyte functionality, positioning adipose tissue as a critical target for metabolic diseases resulting from Cd exposure.

Alpha-Linolenic Acid Ameliorates Cognitive Impairment and Liver Damage Caused by Obesity.

Obesity is a growing global problem that causes various complications such as diabetes, cognitive dysfunction, cardiovascular diseases, and hepatobiliary disease. Alpha-linolenic acid (ALA) has been reported to exhibit multiple pharmaceutical effects. This study aimed to explore the effects of ALA on obesity-induced adipose tissue accumulation, cognitive impairment, inflammation, and colonic mucosal barrier integrity. Mice were fed with high-fat diet (HFD) and were treated with ALA (60 or 100 mg/kg). Body weight, adipose tissue, serum glucose and lipid levels, glucose resistance, and insulin resistance were measured. Cognitive ability was analyzed using the behavior tests. PTP1B and IRS/p-AKT/p-GSK3β/p-Tau signaling were examined to evaluate inflammation and synaptogenesis. Colon mucosal barrier integrity was examined by Alcian blue staining and expression of the tight junction proteins. The production of pro-inflammatory cytokines and liver damages were evaluated. 3T3-L1 cells were used for in vitro experiments. Cell viability, migration and invasion were detected. The levels of ROS, iron, and ferrous ions were measured to assess ferroptosis. Metabolomic analysis of adipose tissues was performed. ALA treatment prevented HFD-induced adipose tissue accumulation, improved glucose and lipid homeostasis and metabolism. Administration of ALA repressed the HFD-induced increase in insulin levels and insulin resistance index. Serum and colon levels of pro-inflammatory cytokines were decreased after ALA treatment. ALA elevated mitochondrial content in brown adipose tissues. ALA ameliorated obesity-induced cognitive impairment and hippocampal inflammation, enhanced colon mucosa integrity. ALA treatment ameliorated HFD-induced liver damage and lipid accumulation and inhibited differentiation of preadipocyte 3T3-L1 cells into mature adipocytes and induces ferroptosis. Metabolomic analysis suggested that ALA may target the glycerolipid metabolism pathway to ameliorate obesity. Knockdown of AGPAT2 abolished the protective effects of ALA. ALA treatment suppressed adipose accumulation in adipocytes, improved cognitive ability and colon integrity, and alleviated liver damage by modulating the 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2).

Ilex paraguariensis A.St.-Hil. improves lipid metabolism in high-fat diet-fed obese rats and suppresses intracellular lipid accumulation in 3T3-L1 adipocytes via the AMPK-dependent and insulin signaling pathways.

Obesity is closely associated with several chronic diseases, and adipose tissue plays a major role in modulating energy metabolism. This study aimed to determine whether Mate, derived from I. paraguariensis A.St.-Hil., ameliorates lipid metabolism in 3T3-L1 adipocytes and high-fat diet (HFD)-fed obese Sprague-Dawley (SD) rats. 3T3-L1 adipocytes were cultured for 7 days, following which intracellular lipid accumulation and expression levels of lipid metabolism-related factors were examined. Dorsomorphin was used to investigate the potential pathways involved, particularly the adenosine monophosphate-activated protein kinase (AMPK)- dependent pathway. Mate was administered to rat HFD-fed obese SD models for 8 consecutive weeks. The expression of lipid metabolism-related factors in the organs and tissues collected from dissected SD rats was evaluated. Mate suppressed intracellular lipid accumulation in 3T3-L1 adipocytes, increased the protein and gene expression levels of AMPK, hormone sensitive lipase (HSL), calmodulin kinase kinase (CaMKK), liver kinase B1 (LKB1), protein kinase A (PKA), CCAAT/enhancer binding protein β (C/EBPβ), insulin receptor b (IRβ), and insulin receptor substrate 1 (IRS1) (Tyr465), and decreased those of sterol regulatory element binding protein 1C (Srebp1c), fatty acid synthase (FAS), peroxisome-activated receptor γ (PPARγ), and IRS1 (Ser1101). Furthermore, an AMPK inhibitor abolished the effects exerted by Mate on intracellular lipid accumulation and HSL and FAS expression levels. Mate treatment suppressed body weight gain and improved serum cholesterol levels in HFD-fed obese SD rats. Treatment with Mate increased the protein and gene expression levels of AMPK, PKA, Erk1/Erk2 (p44/p42), and uncoupling protein 1 and reduced those of mammalian target of rapamycin, S6 kinase, Srebp1c, ap2, FAS, Il6, Adiponectin, Leptin, and Fabp4 in rat HFD-fed obese SD models. Mate suppressed intracellular lipid accumulation in 3T3-L1 adipocytes and improved lipid metabolism in the epididymal adipose tissue of HFD-fed obese SD rats via the activation of AMPK-dependent and insulin signaling pathways.

Metabolic effects of aldosterone

Currently, increasing evidence shows the mutual influence of aldosterone and adipose tissue. Aldosterone excess has been reported in patients with obesity and metabolic syndrome. Aldosterone has a direct effect on adipose tissue increasing anabolic activity and expression of mineralocorticoid receptors. In turn, excessive activation of MCR leads to stimulation of adipogenesis and an increase in the volume of adipose tissue. Aldosterone excess can be considered an independent cardiovascular risk factor that affects such processes as cardiac fibrosis, nephrosclerosis, and arteriosclerosis. There is convincing evidence of higher prevalence and severity of impaired glucose homeostasis and lipid metabolism disorders among patients with primary hyperaldosteronism. Similar pathological changes are also observed in patients with obesity and metabolic syndrome. This review presents scientific data on the metabolic effects of aldosterone, in particular its effect on adipose tissue function, glucose and lipid metabolism. Treatment with mineralocorticoid receptor antagonists may provide substantial benefit in the management of metabolic syndrome, contribute to the stabilisation of glucose and lipid metabolism, improve clinical status of patients with cardiovascular diseases and reduce the risk of complications. However, available evidence from the conducted studies is not sufficient to justify introduction of such therapy into clinical practice.

Metabolic remodeling of visceral and subcutaneous white adipose tissue during reacclimation of rats after cold.

Deciphering lipid metabolism in white adipose tissue (WAT) depots during weight gain is important to understand the heterogeneity of WAT and its roles in obesity. Here, we examined the expression of key enzymes of lipid metabolism and changes in the morphology of representative visceral (epididymal) and subcutaneous (inguinal) WAT (eWAT and iWAT, respectively)-in adult male rats acclimated to cold (4 ± 1°C) for 45 days and reacclimated to room temperature (RT, 22 ± 1°C) for 1, 3, 7, 12, 21, or 45 days. The relative mass of both depots decreased to a similar extent after cold acclimation. However, fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), and medium-chain acyl-CoA dehydrogenase (ACADM) protein level increased only in eWAT, whereas adipose triglyceride lipase (ATGL) expression increased only in iWAT. During reacclimation, the relative mass of eWAT reached control values on day 12 and that of iWAT on day 45 of reacclimation. The faster recovery of eWAT mass is associated with higher expression of FAS, acetyl-CoA carboxylase (ACC), G6PDH, and ACADM during reacclimation and a delayed increase in ATGL. The absence of an increase in proliferating cell nuclear antigen suggests that the observed depot-specific mass increase is predominantly due to metabolic adjustments. In summary, this study shows a differential rate of visceral and subcutaneous adipose tissue weight regain during post-cold reacclimation of rats at RT. Faster recovery of the visceral WAT as compared to subcutaneous WAT during reacclimation at RT could be attributed to observed differences in the expression patterns of lipid metabolic enzymes.

Effect of Fructose on lipoprotein lipase in brown adipose tissue

The per capita intake of fructose mostly in the form of high fructose corn syrup has increased 4- to 5-fold in recent decades. To determine the impact of dietary fructose on parameters of lipid metabolism in brown adipose tissue in T2DM rats, groups of lean and obese-T2DM rats were fed a nutritionally adequate diet consisting of 54% carbohydrate as either cooked cornstarch (CS) or equal parts CS and fructose (CSF diet) from one until 9 months of age. Measures of initial and final body weight s were recorded. At 9 months of age, measures of interscapular brown adipose tissue mass, and size, number, lipoprotein lipase activity, and lipid content determined. Data were analyzed by ANOVA. The body weights of lean and obese littermates were similar at 4 weeks of age, but the net weight gain of the obese phenotype over the 8 months of observation was twice that of their lean littermates, (p = < 0.01). The IBAT mass of obese rats >> than their lean littermates and was not affected by diet in either phenotype. The IBAT number / depot and lipid content / cell and percent lipid / IBAT depot was greater in obese than lean and was not affected by diet. The IBAT LPL activity of obese >> lean and was greater with the CSF than the CS diet in both phenotypes. In conclusion, these results indicate that the obese phenotype results in marked increases in IBAT mass and cellularity independently of diet. LPL activity of lean >> obese and was increased modestly in both phenotypes with the CSF diet. Thus, long term consumption of an isoenergetic diet high in fructose modulates LPL activity and lipid accumulation in brown adipose tissue in a rodent model of insulin resistance and NIDDM. In addition, the expression of obesity in the obese phenotype is more likely a result of the epigenetic metabolic determinants of obesity rather than the specific type of the dietary carbohydrate consumed per se.

Spermidine activates adipose tissue thermogenesis through autophagy and fibroblast growth factor 21

Spermidine exerts protective roles in obesity, while the mechanism of spermidine in adipose tissue thermogenesis remains unclear. The present study first investigated the effect of spermidine on cold-stimulation and β3-adrenoceptor agonist-induced thermogenesis in lean and high-fat diet-induced obese mice. Next, the role of spermidine on glucose and lipid metabolism in different types of adipose tissue was determined. Here, we found that spermidine supplementation did not affect cold-stimulated thermogenesis in lean mice, while significantly promoting the activation of adipose tissue thermogenesis under cold stimulation and β3-adrenergic receptor agonist treatment in obese mice. Spermidine treatment markedly enhanced glucose and lipid metabolism in adipose tissues, and these results were associated with the activated autophagy pathway. Moreover, spermidine up-regulated fibroblast growth factor 21 (FGF21) signaling and its downstream pathway, including PI3K/AKT and AMPK pathways in vivo and in vitro. Knockdown of Fgf21 or inhibition of PI3K/AKT and AMPK pathways in brown adipocytes abolished the thermogenesis-promoting effect of spermidine, suggesting that the effect of spermidine on adipose tissue thermogenesis might be regulated by FGF21 signaling via the PI3K/AKT and AMPK pathways. The present study provides new insight into the mechanism of spermidine on obesity and its metabolic complications, thereby laying a theoretical basis for the clinical application of spermidine.

Arsenic and adipose tissue: an unexplored pathway for toxicity and metabolic dysfunction.

Arsenic-contaminated drinking water can induce various disorders by disrupting lipid and glucose metabolism in adipose tissue, leading to insulin resistance. It inhibits adipocyte development and exacerbates insulin resistance, though the precise impact on lipid synthesis and lipolysis remains unclear. This review aims to explore the processes and pathways involved in adipogenesis and lipolysis within adipose tissue concerning arsenic-induced diabetes. Although arsenic exposure is linked to type 2 diabetes, the specific role of adipose tissue in its pathogenesis remains uncertain. The review delves into arsenic's effects on adipose tissue and related signaling pathways, such as SIRT3-FOXO3a, Ras-MAP-AP-1, PI(3)-K-Akt, endoplasmic reticulum stress proteins, CHOP10, and GPCR pathways, emphasizing the role of adipokines. This analysis relies on existing literature, striving to offer a comprehensive understanding of different adipokine categories contributing to arsenic-induced diabetes. The findings reveal that arsenic detrimentally impacts white adipose tissue (WAT) by reducing adipogenesis and promoting lipolysis. Epidemiological studies have hinted at a potential link between arsenic exposure and obesity development, with limited research suggesting a connection to lipodystrophy. Further investigations are needed to elucidate the mechanistic association between arsenic exposure and impaired adipose tissue function, ultimately leading to insulin resistance.

A review of the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle.

In the past few decades, genomic selection and other refined strategies have been used to increase the growth rate and lean meat production of beef cattle. Nevertheless, the fast growth rates of cattle breeds are often accompanied by a reduction in intramuscular fat (IMF) deposition, impairing meat quality. Transcription factors play vital roles in regulating adipogenesis and lipogenesis in beef cattle. Meanwhile, understanding the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle has gained significant attention to increase IMF deposition and meat quality. Therefore, the aim of this paper was to provide a comprehensive summary and valuable insight into the complex role of transcription factors in adipogenesis and lipogenesis in beef cattle. This review summarizes the contemporary studies in transcription factors in adipogenesis and lipogenesis, genome-wide analysis of transcription factors, epigenetic regulation of transcription factors, nutritional regulation of transcription factors, metabolic signalling pathways, functional genomics methods, transcriptomic profiling of adipose tissues, transcription factors and meat quality and comparative genomics with other livestock species. In conclusion, transcription factors play a crucial role in promoting adipocyte development and fatty acid biosynthesis in beef cattle. They control adipose tissue formation and metabolism, thereby improving meat quality and maintaining metabolic balance. Understanding the processes by which these transcription factors regulate adipose tissue deposition and lipid metabolism will simplify the development of marbling or IMF composition in beef cattle.

Body weight gain and control: beneficial effect of extra virgin olive oil versus corn oil in an experimental model of mammary cancer

Obesity is a known risk factor for breast cancer, the most common malignancy among women worldwide. We have previously described different effects of high-fat diets on mammary experimental carcinogenesis. In this work, we analyzed the animal growth data obtained in six experimental assays, in healthy and carcinogen-induced rats undergoing different dietary interventions. The animals were fed with three experimental diets administered at different periods of development: a control low-fat diet, and two isocaloric high-fat diets (rich in corn oil or in extravirgin olive oil -EVOO-). Weekly weight throughout the development of 818 animals have been compiled and reanalyzed using adjusted mathematical models. Molecular mechanisms have been investigated: ethanolamides in small intestine, neuropeptides controlling satiety in hypothalamus, and proteins controlling lipid metabolism in adipose and mammary tissues. The results indicated that the effect of diets depended on type of lipid, timing of intervention and health status. The high corn oil diet, but not the high EVOO diet, increased body weight and mass, especially if administered from weaning, in healthy animals and in those that received a moderate dose of carcinogen. The potential protective effect of EVOO on weight maintenance may be related to anorexigenic neuropeptides such as oxytocin and lipolysis/deposition balance in adipose tissue (increasing phospho-PKA, HSL, MGL and decreasing FAS). In animals with cancer, body weight gain was related to the severity of the disease. Taken together, our results suggest that EVOO has a beneficial effect on body weight maintenance in both health and cancer.

Age-Related Changes in Hepatic Lipid Metabolism and Abdominal Adipose Deposition in Yellow-Feathered Broilers Aged from 1 to 56 Days.

The objective of this study was to evaluate the age-related changes in hepatic lipid metabolism, adipocyte hyperplasia, hypertrophy, and lipid metabolism in the abdominal adipose tissue of yellow-feathered broilers. Blood, liver, and abdominal adipose samples were collected on days 1, 7, 14, 21, 28, 35, 42, 49, and 56. Body, liver, and abdominal weight increased (p < 0.05) with age-related changes. The triacylglycerol content peaked on day 14, and total cholesterol content peaked on day 56. The adipocyte diameter and area peaked on day 56, and total DNA content peaked on day 7. The age-related changes in hepatic lipogenesis-related gene (ChREBP, SREBP-1c, ACC, FAS, SCD1) expression mainly occurred during days 1 to 21, hepatic lipolysis-related gene (CPT1, LPL, ApoB) expression mainly occurred during days 1 to 14, and abdominal adipose-deposition-related gene (PPARα, CPT1, LPL, PPARγ, C/EBPβ) expression occurred during days 1 to 14. These results demonstrated a dynamic pattern of hepatic lipid metabolism and abdominal adipose deposition in yellow-feathered broilers, which provides practical strategies to regulate hepatic lipid metabolism and reduce abdominal adipose deposition in yellow-feathered broilers.

Flavonoids from mulberry leaves inhibit fat production and improve fatty acid distribution in adipose tissue in finishing pigs

This study evaluated the effects of flavonoids from mulberry leaves (FML) on plasma biochemical indices, serum activities of lipid metabolism-related enzymes, fat morphology, fatty acid composition, and lipid metabolism in different adipose tissues of finishing pigs. We used 120 Chinese hybrid barrows of Berkshire and Bama mini-pigs with an average initial body weight of 45.11 ± 4.23 kg. The pigs were randomly assigned to five treatment groups and fed a control diet based on corn, soybean meal, and wheat bran or a control diet supplemented with 0.02%, 0.04%, 0.08%, or 0.16% FML. Each experimental group had six replicates (pens), with four pigs per pen. After a 7-d adaptation period, the feeding trial was conducted for 58 d. Blood and adipose tissue samples were collected from 30 pigs (one pig per pen) at the end of the test. The results showed that FML supplementation significantly decreased the feed intake to body gain ratio, the plasma concentrations of total cholesterol and free fatty acids, and the serum activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (linear or quadratic effects, P < 0.05), and decreased the plasma triglyceride concentration (quadratic, P = 0.07). Increasing FML supplementation increased the average daily gain and serum activities of lipoprotein lipase (linear and quadratic effects, P < 0.05) and adipose triglyceride lipase (linear, P < 0.05). Dietary FML supplementation decreased the adipocyte area in the dorsal subcutaneous adipose (DSA) tissue of finishing pigs (linear, P = 0.05) and increased the adipocyte area in the visceral adipose tissue (quadratic, P < 0.01). Increasing FML supplementation decreased the C20:1 content in DSA, abdominal subcutaneous adipose, and visceral adipose tissues of finishing pigs (P < 0.05) and increased the C18:3n3 and n-3 PUFA contents (P < 0.05). The lipid metabolism genes were regulated by the PPARγ-LXRα-ABCA1 signaling pathway, and their expressions differed in different adipose tissues. These findings suggest that FML improved growth performance, regulated lipid metabolism, inhibited fat production, and improved fatty acid distribution in the adipose tissue of finishing pigs, thereby improving pig fat's nutritional quality and health value.

Succinate Enhances Lipolysis and Decreases Adipocytes Size in Both Subcutaneous and Visceral Adipose Tissue from High-Fat-Diet-Fed Obese Mice.

Obesity is a risk factor for many chronic diseases related to the overexpansion of adipose tissue during obesity, leading to metabolic dysfunction and ectopic lipids. Previous studies reported a close relationship between succinate and obesity and its co-morbidities, and studies have also reported on its anti-obesity potential. To confirm its efficacy in obesity interventions, we supplemented mice with obesity induced by a high-fat diet with succinate (1.5% m/v in drinking water) for 11 weeks without changing the diet. After succinate supplementation, the changes in body weight, adipose tissue deposition, glucose tolerance, energy expenditure and lipid metabolism were evaluated. It was found that succinate supplementation significantly decreased subcutaneous adipose tissue (HFD: 4239.3 ± 211.2 mg; HFD-SA: 3268.9 ± 265.7 mg. p < 0.05), triglyceride contents (decreased by 1.53 mmol/g and 0.39 mmol/g in eWAT and ingWAT, respectively, p < 0.05) and NEFA (decreased by 1.41 μmol/g and 1.31 μmol/g in eWAT and ingWAT, respectively, p < 0.05). The adipocytes' sizes all significantly decreased in both subcutaneous and visceral adipose tissue (the proportion of adipocytes with diameters larger than 100 μm in eWAT and ingWAT decreased by 16.83% and 11.96%, respectively. p < 0.05). Succinate significantly enhanced lipolysis in adipose tissue (eWAT: Adrb3, Hsl and Plin1; ingWAT: Hsl and CPT1a; p < 0.05), whereas the expression of lipogenesis-related genes remained unchanged (p > 0.05). Succinate supplementation also enhanced the activity of BAT by stimulating the expression of Ucp1 and Cidea (p < 0.05). Our results reported that succinate has a potential beneficial effect on obesity pathogenesis but cannot efficiently decrease bodyweight.

Circadian organization of lipid landscape is perturbed in type 2 diabetic patients

Lipid homeostasis in humans follows a diurnal pattern in muscle and pancreatic islets, altered upon metabolic dysregulation. We employ tandem and liquid-chromatography mass spectrometry to investigate daily regulation of lipid metabolism in subcutaneous white adipose tissue (SAT) and serum of type 2 diabetic (T2D) and non-diabetic (ND) human volunteers (n= 12). Around 8% of≈440 lipid metabolites exhibit diurnal rhythmicity in serum and SAT from ND and T2D subjects. The spectrum of rhythmic lipids differs between ND and T2D individuals, with the most substantial changes observed early morning, as confirmed by lipidomics in an independent cohort of ND and T2D subjects (n= 32) conducted at a single morning time point. Strikingly, metabolites identified as daily rhythmic in both serum and SAT from T2D subjects exhibit phase differences. Our study reveals massive temporal and tissue-specific alterations of human lipid homeostasis in T2D, providing essential clues for the development of lipid biomarkers in a temporal manner.

DHA promotes healthy adipose tissue remodeling and carbohydrate utilization in grass carp (Ctenopharyngodon idellus) and largemouth bass (Micropterus salmoides)

Due to the wide usage of high-carbohydrate diets in aquaculture, improving the ability of fish to utilize high-carbohydrate diets is one of the important issues in aquaculture. Adipose tissue is an essential organ for storing energy and plays a vital role in glucose homeostasis. In this study, RNA sequencing reveals that docosahexaenoic acid (DHA) promoted the expression of the glucose metabolism related-genes in grass carp adipocytes, raising the hypothesis that DHA may attenuate the adverse effect of high-carbohydrate diets on fish via promoting glucose metabolism in adipose tissue. To verify this hypothesis, a total of 180 juvenile grass carp (14.24 ± 0.43 g) and a total of 180 largemouth bass (40.03 ± 0.12 g) were randomly distributed into 18 tanks (200 L), respectively, and fed with high-carbohydrate diets containing DHA. The results showed that high-carbohydrate diets promoted glycolysis and inhibited lipolysis and fatty acid β-oxidation, leading to the excessive accumulation of abdominal fat and adipose tissue inflammation. After feeding high-carbohydrate diets supplementation with DHA, glucose transporter type 4 (GLUT4) mediated-glucose uptake was increased in adipose tissue, resulting in significantly decreased blood glucose in grass carp and largemouth bass (P < 0.05). And then, the glucose was converted to triglyceride through the glucose-6-phosphate dehydrogenase (G6PD) mediated-pentose phosphate pathway, de novo synthesis of fatty acids and triglyceride (TG) synthesis. Subsequently, the resulting TG was broken down through lipolysis and fatty acid β-oxidation. These reprogrammed metabolic processes inhibited the excessive accumulation of abdominal fat. In addition, DHA attenuated inflammation in adipose tissue, and further reduced the levels of inflammatory cytokines in serum (P < 0.05), indicating that DHA promotes healthy adipose tissue remodeling. Ultimately, these benefits improved the growth performance of grass carp and largemouth bass fed with high-carbohydrate diets. Taken together, our study indicates that adipose tissue is an important target for improving the negative effects of high-carbohydrate diets, and DHA could promote healthy adipose tissue remodeling and improve carbohydrate utilization in fish by reprogramming the glucose and lipid metabolism in adipose tissues.