Tissue Lipid Research Articles

GDF15 is required for maintaining subcutaneous adipose tissue lipid metabolic signature

Recent research has identified growth differentiation factor 15 (GDF15) as a crucial factor in various physiological and pathological processes, particularly in energy balance regulation. While the role of GDF15 in modulating energy metabolism through hindbrain GDNF family receptor alpha-like (GFRAL) signaling has been extensively studied, emerging evidence suggests direct peripheral metabolic actions of GDF15. Using knockout mouse models, we investigated GDF15 and GFRAL’s roles in adipose tissue metabolism. Our findings indicate that C57BL/6/129/SvJ Gdf15-KO mice exhibit impaired expression of de novo lipogenesis enzymes in subcutaneous adipose tissue (sWAT). In contrast, C57BL/6J Gfral-KO mice showed no impairments compared to wild-type (WT) littermates. RNA-Seq analysis of sWAT in Gdf15-KO mice revealed a broad downregulation of genes involved in lipid metabolism. Importantly, our study uncovered sex-specific effects, with females being more affected by GDF15 loss than males. Additionally, we observed a fasting-induced upregulation of GDF15 gene expression in sWAT of both mice and humans, reinforcing this factor’s role in adipose tissue lipid metabolism. In conclusion, our research highlights an essential role for GDF15 in sWAT lipid metabolic homeostasis. These insights enhance our understanding of GDF15’s functions in adipose tissue physiology and underscore its potential as a therapeutic target for metabolic disorders.

Euglena Attenuates High-Fat-Diet-Induced Obesity and Especially Glucose Intolerance.

Background: Obesity, a global disease, can lead to different chronic diseases and a series of social health problems. Lifestyle changes, especially dietary changes, are the most effective way to treat obesity. Euglena, a novel food, has attracted much attention. Previous studies have shown that Euglena is an important modulator of the host immune response. In this study, the effects of Euglena as a nutritional intervention in high-fat-diet-induced obese C57BL/6J mice were investigated regarding adipose tissue accumulation and lipid and glucose metabolism by gavage at the dose of 100 mg/kg bodyweight for 9 weeks. This study is one of the few to investigate, in detail, the preventive effects of dietary Euglena on obesity. Methods: Five-week-old male C57BL/6J mice were fed with a high-fat diet (HFD) to induce obesity. An obesity model was created by feeding the high-fat diet for a period of 10 weeks. Obese mice were randomized into 2 groups with the same mean body weight, and no significant differences were observed between the groups: (1) the mice in the HEG group were maintained on a high-fat diet and daily gavaged with Euglena (100 mg/kg body weight) dissolved in saline (n = 7); and (2) the mice in the HFD group were maintained on a high-fat diet and daily gavaged with saline with the same volume (n = 7). The experiment finished after a nine-week period. Results: The results showed that Euglena could reduce the accumulation of white body fat, including subcutaneous fat and visceral fat, and mainly targeted subcutaneous fat. Euglena also reduced adipocyte particle size expansion, promoted lipolysis in adipose (adipose triglyceride lipase and hormone-sensitive triglyceride lipase) and liver tissue (reduced non-esterified fatty acid content), and improved obesity-induced ectopic fat deposition and glucose tolerance. Conclusions: Our findings suggest that Euglena, as a nutritional intervention in HFDs, efficiently reduces body weight and white adipose tissue deposition. The mechanism of Euglena is mainly though enhancing lipolysis. It is worth noting that Euglena β-glucan recovers the hyperglycemia and accumulation of ectopic fat within the liver induced by HFD. Our study is one of the few studies to report in detail the preventive effects of dietary Euglena on obesity in vivo. This study revealed that Euglena also has an important ameliorative effect on obesity and metabolic disorders, which laid a theoretical foundation for its future application in functional foods.

Metabolic Effects of Loquat Juice (Eriobotrya japonica Lindl Mkarkeb Variety) on Lipid Homeostasis, Liver Steatosis, and Oxidative Stress in Hyperlipidemic Mice Fed a High-Fat–High-Fructose Diet

Background: Loquat fruit is consumed for its flavorful taste and a rich array of health-promoting compounds like phenolics, flavonoids, and carotenoids. This study aimed at the biochemical characterization of fresh juice from the Moroccan Mkarkeb variety of loquat and evaluating its effects on lipid homeostasis and liver steatosis in hyperlipidemic mice. Methods: The biochemical characterization followed AOAC methods. In vivo study involved hyperlipidemic mice fed a high-fat, high-fructose diet for 6 weeks and treated with loquat juice at 3.5 and 7 mL kg−1 or fenofibrate at 4 mg·kg−1. The concentrations of lipids in plasma, liver, adipose tissue, feces, and bile and blood glucose levels were quantified. Liver steatosis was visually examined and confirmed histologically, and liver injury markers (AST, ALT, ALP, LDH, and TB) were measured. Liver oxidative stress was assessed by measuring MDA content and antioxidative enzyme activities. Results: Our findings indicate that fresh loquat juice is poor in fat and protein and contains moderate sugars with a low energy value (40.82 ± 0.25 kcal/100 g). It is also rich in minerals, vitamin C, phenolic acids, flavonoids, and carotenoids. The juice effectively restored lipid metabolism by enhancing reverse cholesterol transport and lowering LDL-cholesterol, triglycerides, and the atherogenic index. The studied juice decreases blood glucose and prevents weight gain and lipid accumulation in the liver and adipose tissue. The juice prevents lipotoxicity-induced liver injury, corrects toxicity markers, and improves the liver’s morphological and histological structures. It also reduces oxidative stress by lowering MDA and activating SOD and catalase. Conclusions: The juice holds high nutritional and medicinal value, potentially preventing lipid disorders and cardiovascular issues.

Characterization of methanolysis products from plasmalogenic lipids in horse muscle tissue

Muscle tissue is known to contain plasmalogenic lipids. Traditional methodologies for the analysis of lipids in muscle consists of methanolysis followed by gas chromatography (GC). The resultant dimethylacetals (DMA) are difficult to resolve because of extensive overlap with fatty acid methyl esters. In this study a new two-step procedure was applied to isolate DMAs from FAMEs from methanolysed horse muscle lipids (n=48) after saponification and solvent partitioning. Both total and isolated DMAs were analysed by GC and the extent of overlap was evident. The total methylated mixture was also analyzed using GC with online reduction (GC-OR x GC) which confirmed the identity of the FAME, DMA and aldehyde products. The DMA content in horse muscle tissue was found to be 55.7mg DMAs in 100g of meat, or 3.10% of total lipids. The saturates 16:0 and 18:0 were the predominant DMA isomers, and 18:3n-3 and 18:2n-6 DMA were identified in this tissue. Samples with a higher (> 3g/100g of meat) intramuscular fat (IM) content showed a lower (p ≤ 0.05) absolute content of the DMAs compared to samples with lower IM fat content (15.3 vs 29.3mg/g of fat, respectively).

Ethnic differences in the relationship between ectopic fat deposition and insulin sensitivity in Black African and White European men across a spectrum of glucose tolerance.

To examine the hypothesis that there would be ethnic differences in the relationship between ectopic fat and tissue-specific insulin resistance (IR) across a spectrum of glucose tolerance in Black African (BA) and White European (WE) men. Fifty-three WE men (23/10/20 normal glucose tolerance [NGT]/impaired glucose tolerance [IGT]/type 2 diabetes [T2D]) and 48 BA men (20/10/18, respectively) underwent a two-step hyperinsulinaemic-euglycaemic clamp with infusion of D-[6,6-2H2]-glucose and [2H5]-glycerol to assess hepatic, peripheral and adipose tissue IR. Magnetic resonance imaging was used to measure subcutaneous adipose tissue, visceral adipose tissue (VAT) and intrahepatic lipid (IHL). Associations between ectopic fat and IR were assessed using linear regression models. There were no differences in tissue-specific IR between ethnic groups at any stage of glucose tolerance. VAT level was consistently lower in the BA population; NGT (p = 0.013), IGT (p = 0.006) and T2D (p = 0.015). IHL was also lower in the BA compared with the WE men (p = 0.013). VAT and IHL levels were significantly associated with hepatic IR in the BA population (p = 0.001) and with peripheral IR in the WE population (p = 0.027). The present study suggests that BA and WE men exhibit the same degree of IR across a glucose tolerance continuum, but with lower VAT and IHL levels in the BA population, suggesting that IR may be driven by a mechanism other than increased ectopic fat accumulation in BA men.

Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.

Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential for maintaining physiological functions and metabolic homeostasis. However, chronic elevation of BCAAs causes metabolic diseases such as obesity, type 2 diabetes (T2D), and metabolic-associated fatty liver disease (MAFLD). Adipose tissue, skeletal muscle, and the liver are the three major metabolic tissues not only responsible for controlling glucose, lipid, and energy balance but also for maintaining BCAA homeostasis. Under obese and diabetic conditions, different pathogenic factors like pro-inflammatory cytokines, lipotoxicity, and reduction of adiponectin and peroxisome proliferator-activated receptors γ (PPARγ) disrupt BCAA metabolism, leading to excessive accumulation of BCAAs and their downstream metabolites in metabolic tissues and circulation. Mechanistically, BCAAs and/or their downstream metabolites, such as branched-chain ketoacids (BCKAs) and 3-hydroxyisobutyrate (3-HIB), impair insulin signaling, inhibit adipogenesis, induce inflammatory responses, and cause lipotoxicity in the metabolic tissues, resulting in multiple metabolic disorders. In this review, we summarize the latest studies on the metabolic regulation of BCAA homeostasis by the three major metabolic tissues-adipose tissue, skeletal muscle, and liver-and how dysregulated BCAA metabolism affects glucose, lipid, and energy balance in these active metabolic tissues. We also summarize therapeutic approaches to restore normal BCAA metabolism as a treatment for metabolic diseases.

Metabolic syndrome.

The metabolic syndrome (MetS) is a multiplex modifiable risk factor for cardiovascular disease, type 2 diabetes mellitus and other health outcomes, and is a major challenge to clinical practice and public health. The rising global prevalence of MetS, driven by urbanization, sedentary lifestyles and dietary changes, underlines the urgency of addressing this syndrome. We explore the complex underlying mechanisms, including genetic predisposition, insulin resistance, accumulation of dysfunctional adipose tissue and ectopic lipids in abdominal obesity, systemic inflammation and dyslipidaemia, and how they contribute to the clinical manifestations of MetS. Diagnostic approaches vary but commonly focus on abdominal obesity (assessed using waist circumference), hyperglycaemia, dyslipidaemia and hypertension, highlighting the need for population-specific and phenotype-specific diagnostic strategies. Management of MetS prioritizes lifestyle modifications, such as healthy dietary patterns, physical activity and management of excess visceral and ectopic adiposity, as foundational interventions. We also discuss emerging therapies, including new pharmacological treatments and surgical options, providing a forward-looking perspective on MetS research and care. This Primer aims to inform clinicians, researchers and policymakers about MetS complexities, advocating for a cohesive, patient-centred management and prevention strategy. Emphasizing the multifactorial nature of MetS, this Primer calls for integrated public health efforts, personalized care and innovative research to address this escalating health issue.

Curcumin Modulates the Differential Effects of Fructose and High-Fat Diet on Renal Damage, Inflammation, Fibrosis, and Lipid Metabolism.

Dyslipidemia and obesity hypercaloric diet-induced lead to kidney damage. We investigated the effect of curcumin on the expression of proteins related to inflammation, fibrosis, fatty acids metabolism, kidney damage, and morphological changes in the kidneys of mice hypercaloric diets-fed. Groups of 5-week-old C57BL/6 mice (n=6) were formed: Control (C), High-fructose diet (F), Highfructose diet and curcumin (F+Cur), High-fat diet (HFD), High-fat diet and curcumin (HFD+Cur), High-fat diet and fructose (HFD+F), High-fat diet, fructose and curcumin (HFD+F+Cur), treated for 16 weeks with 30% (w/v) fructose, 60% (w/w) fat and 0.75% (w/w) curcumin. Kidneys were obtained for histomorphological and Western Blot analysis. Curcumin prevented TNF-α overexpression in the F and HFD+F groups. VLCAD expression was higher in the F, HFD, and HFD+F groups. PPARγ expression was lower in the F+Cur, HFD+Cur, and HFD+F+Cur groups. Curcumin prevented overexpression of CPT1 and KIM1 in the HFD+F and HFD groups. Curcumin prevented morphological lesions, fibrosis, and lipid deposition that were hypercaloric diet-induced. Chronic consumption of hypercaloric diets causes inflammation, fibrosis, and lipid deposition in the kidney. It is suggested that curcumin prevents renal structural damage, limits tissue lipid deposition, and differentially modulates renal injury depending on diet composition in mice fed high-fat and/or high-fructose diets.

Fatty Acid Content and Lipid Nutritional Indexes in the Antarctic Krill Euphausia superba Collected from Three Regions of the Atlantic Sector of Antarctica.

The total lipid (TL) and fatty acid (FA) contents in tissues and body segments were studied in adult Antarctic krill (Euphausia superba) caught in three regions of the Atlantic sector of Antarctica with different environmental conditions. Significant differences in lipid and FA status of the Antarctic krill tissues and body segments were observed in the regions. Main metabolic indices indicating quality of lipids showed that E.superba has a high nutritional value. In particular, lipids are highly unsaturated in the species and ratios of physiologically significant and essential FAs are favorable to human health. This was assumed to be a distinctive biochemical characteristic of the species. Data from the study can be used to form a scientifically based approach to further technological processing of raw krill and targeted extraction of certain substances and components of a lipid nature.

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

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

Persistent effects of di-n-butyl phthalate on liver transcriptome: impaired energy and lipid metabolic pathways

The environmental contaminant dibutyl phthalate (DBP) is reported to be hepatotoxic, but the underlying molecular pathways and pathological processes remain unclear. Here we used RNA-sequencing to characterize persistent hepatic transcriptional effects one week after the conclusion of five weeks oral exposure to 10 mg/kg/day or 100 mg/kg/day DBP in male mice. The exploratory transcriptome analysis demonstrated five differentially expressed genes (DEGs) in the 10 mg/kg/day group and thirteen in the 100 mg/kg/day group. Gene Set Enrichment Analysis (GSEA), which identifies affected biological pathways rather than focusing solely on individual genes, revealed nine significantly enriched Reactome pathways shared by both DBP treatment groups. Additionally, we found 54 upregulated and one downregulated Reactome pathways in the 10 mg/kg/day DBP group, and 29 upregulated and 13 downregulated pathways in the 100 mg/kg/day DBP group. According to the DEGs and the GSEA findings DBP exposure disrupts several key biological processes, including protein translation, protein folding, apoptosis, hedgehog signaling, degradation of extracellular matrix and alterations in the energy/lipid metabolism. Subsequent liver tissue analysis corroborated these findings, showing that DBP exposure induced tissue disorganization, oxidative stress, lipid accumulation, increased TNF-α, ATP and glucokinase levels. In addition, several proteins central for the metabolic system were affected, mostly in a dose-response pattern. Taken together the results show that DBP can cause hepatic stress and damage and suggest a potential role for DBP in the development of non-alcoholic fat liver disease, the most prevalent liver disease worldwide.

Effects of the organochlorine pesticide metabolite p,p’-DDE on the gastrointestinal lipidome in fish: A novel toxicity pathway for a legacy pollutant

Though phased out from use in the United States, environmental contamination by organochlorine pesticides (OCPs) remains a widespread issue, especially around intensive agricultural regions. OCPs, such as dichlorodiphenyltrichloroethane (DDT) and its primary metabolite, dichlorodiphenyldichloroethylene (DDE), have been detected in soils, sediments, surface waters, and biota decades after their discontinued use. As OCPs are persistent and can bioaccumulate in fats, these compounds can transfer and magnify across food webs. Freshwater predatory fish and birds can accumulate high OCP concentrations, leading to a myriad of deleterious impacts on organismal health. Studies have found evidence of reproductive disruption in predatory fish, such as the largemouth bass (LMB; Micropterus salmoides), associated with DDT and DDE exposure. DDE can act through estrogenic pathways and induce the expression of estrogenic signals in male animals; however, the molecular mechanism of disruption is unclear. Recently, metabolomics research has revealed corollary relationships between lipid signals and organic pollutant toxicity. Here, a two-month feeding experiment on LMB was conducted to assess the interactions of DDE (as p,p'-DDE) in food with gut and liver lipid signaling. Targeted lipidomic analysis revealed global alterations in the abundance of tissue lipids, especially cholesteryl esters and phospholipids, in LMB exposed to low levels of p,p'-DDE. Results from these studies indicate that p,p'-DDE may act through disruption of normal lipid homeostasis to cause toxicity in freshwater fish.

Adipose Tissue Plasticity: A Comprehensive Definition and Multidimensional Insight.

Adipose tissue is composed of adipocytes, stromal vascular fraction, nerves, surrounding immune cells, and the extracellular matrix. Under various physiological or pathological conditions, adipose tissue shifts cellular composition, lipid storage, and organelle dynamics to respond to the stress; this remodeling is called "adipose tissue plasticity". Adipose tissue plasticity includes changes in the size, species, number, lipid storage capacity, and differentiation function of adipocytes, as well as alterations in the distribution and cellular composition of adipose tissue. This plasticity has a major role in growth, obesity, organismal protection, and internal environmental homeostasis. Moreover, certain thresholds exist for this plasticity with significant individualized differences. Here, we comprehensively elaborate on the specific connotation of adipose tissue plasticity and the relationship between this plasticity and the development of many diseases. Meanwhile, we summarize possible strategies for treating obesity in response to adipose tissue plasticity, intending to provide new insights into the dynamic changes in adipose tissue and contribute new ideas to relevant clinical problems.

Acute cardiorenal dysfunctions induced by isoprenaline in Wistar rats: Mitigating potential of Juglans regia hull extract

The present study aimed to determine the attenuating properties of Juglans regia hull extract (JRHE) in mitigating isoprenaline (ISO) induced cardiorenal dysfunctions in Wistar rats. Thirty adult Wistar rats were randomly allocated to five groups with six animals in each group. Group I served as control; group II animals were administered ISO and group III received JRHE alone whereas group IV and V received JRHE and quercetin along with ISO, respectively. Administration of ISO in rats induced cardiac and renal tissue damage as reflected by significantly (p < 0.05) increased plasma activities of creatine kinase-myocardial band, lactate dehydrogenase, acetylcholinesterase, arylesterase, blood urea nitrogen, creatinine along with altered antioxidant biomarkers viz. total antioxidant status, total thiols, superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and increased (p < 0.05) lipid and protein peroxidation in cardiac and renal tissues. Histopathological findings corroborated that ISO has inflicted significant damage on cardiac and renal tissues. Repeated administration of JRHE significantly (p < 0.05) reduced the severity of ISO-induced alterations in blood, cardiac and renal biomarkers. In addition to restoring the levels of altered cardio-renal antioxidant enzymes, JRHE also ameliorated histopathological lesions in cardiac and renal tissues in ISO-treated rats.

Biochemical contents of tapeworm Proteocephalus osculatus and its definitive host, Silurus triostegus

The current study dealt with the determination of the concentration of some biomolecules in the tissues of the tapeworm and the intestinal tissue of its definitive host (fish). At the probability level (P≤0.05) a sig-nificant difference was noticed in the concentration of proteins, glycogen and lipids in the intestinal tissue of non-infected fish compared to the infected fish. The concentration of proteins and glycogen in the tissues of the tapeworm was (9.95 and 7.33) mg/g of fresh weight respectively, it was lower than that in the intestinal tissues of its infected definitive host, which amounted to (22.06, 12.33) mg/g of fresh weight, respectively, while lipids appeared in a higher concentration in the tapeworm tissues (19.17) mg/g of fresh weight com-pared to its concentration in the intestine of its infected definitive host (17.10) mg/g of fresh weight. As for the concentration of urea and creatinine, it was found a significant difference at the level of probability (P≤0.05) in the serum of infected and non-infected fish, as both urea and creatinine showed a significant relative increase in the serum of infected fish (12.30, 2.31) mg/dl respectively than in non-infected fish (10.66 and 1.07) mg/dl respectively. Keywords: creatinine; glycogen; lipid; protein; Silurus triostegus; tapeworm; urea

Cold induces brain region-selective cell activity-dependent lipid metabolism.

It has been well documented that cold is an enhancer of lipid metabolism in peripheral tissues, yet its effect on central nervous system lipid dynamics is underexplored. It is well recognized that cold acclimations enhance adipocyte functions, including white adipose tissue (WAT) lipid lipolysis and beiging, and brown adipose tissue (BAT) thermogenesis in mammals. However, it remains unclear whether and how lipid metabolism in the brain is also under the control of cold acclimations. Here, we show that cold exposure predominantly increases the expressions of the lipid lipolysis genes and proteins within the paraventricular nucleus of the hypothalamus (PVH). Mechanistically, we find that cold activates cells within the PVH and pharmacological inactivation of cells blunts cold-induced effects on lipid peroxidation, accumulation of lipid droplets (LDs), and lipolysis in the PVH. Together, these findings suggest that PVH lipid metabolism is cold sensitive and integral to cold-induced broader regulatory responses.

Identifying biochemical changes in the kidney using proton nuclear magnetic resonance in an adenine diet chronic kidney disease mouse model.

This study aimed to investigate the metabolic changes in the kidneys in a murine adenine-diet model of chronic kidney disease (CKD). Kidney fibrosis is the common pathological manifestation across CKD aetiologies. Sustained inflammation and fibrosis cause changes in preferred energy metabolic pathways in the cells of the kidney. Kidney cortical tissue from mice receiving a control or adenine-supplemented diet for 8weeks (late inflammation and fibrosis) and 12 weeks (8weeks of treatment followed by 4weeks recovery) were analysed by 2D-correlated nuclear magnetic resonance spectroscopy and compared with histopathology and biomarkers of kidney damage. Tissue metabolite and lipid levels were assessed using the MestreNova software. Expression of genes related to inflammation, fibrosis, and metabolism were measured using quantitative polymerase chain reaction. Animals showed indicators of severely impaired kidney function at 8 and 12 weeks. Significantly increased fibrosis was present at 8weeks but not in the recovery group suggesting some reversal of fibrosis and amelioration of inflammation. At 8weeks, metabolites associated with glycolysis were increased, while lipid signatures were decreased. Genes involved in fatty acid oxidation were decreased at 8weeks but not 12 weeks while genes associated with glycolysis were significantly increased at 8weeks but not at 12 weeks. In this murine model of CKD, kidney fibrosis was associated with the accumulation of triglyceride and free lactate. There was an up-regulation of glycolytic enzymes and down-regulation of lipolytic enzymes. These metabolic changes reflect the energy demands associated with progressive kidney disease where there is a switch from fatty acid oxidation to that of glycolysis.

Oral Administration of Lutein Improves Fat Graft Survival by Alleviating Oxidative Stress in Mice.

Oxidative stress induced by ischemia and hypoxia in fat transplantation is a major obstacle to graft retention. Previous studies have shown that lutein has excellent adipose tissue affinity and anti-oxidative stress ability, however, the effects of oral lutein on fat transplantation have not been studied yet. We aimed to investigate whether oral lutein can improve fat transplantation retention by regulating oxidative stress, apoptosis, and inflammatory cytokine levels in graft tissues. Nude mice were assigned to the control group (normal saline), low-dose lutein group (10 mg/kg/day) and high-dose lutein group (20 mg/kg/day) randomly. All mice were given by gavage 1 week before fat grafting and continued for 2 weeks. The grafts were collected 1, 2, and 12 weeks after treatment. By conducting histological analyses, western blotting, quantitative polymerase chain reaction and cell metabolic function detections, the regulatory effects of lutein on apoptosis and oxidative stress in grafts were demonstrated. Besides, RNA sequencing was conducted to further clarify the efficacy of lutein on fat grafting. Lutein induced superior graft retention, histological structures and more viable adipocytes than control group. It relieved tissue oxidative stress and lipid oxidative damage by decreasing reactive oxygen species, and significantly reduced inflammation and apoptosis of grafts. RNA sequencing analysis confirmed that lutein could down-regulate the genes expression of oxidative stress and related inflammation and apoptosis. Our study suggested that oral administration of lutein can improve fat graft survival by reducing the levels of oxidative stress, inflammation and apoptosis in grafted fat.

New concepts in the roles of AMPK in adipocyte stem cell biology.

Obesity is a major risk factor for many life-threatening diseases. Adipose tissue dysfunction is emerging as a driving factor in the transition from excess adiposity to comorbidities such as metabolic-associated fatty liver disease, cardiovascular disease, Type 2 diabetes and cancer. However, the transition from healthy adipose expansion to the development of these conditions is poorly understood. Adipose stem cells, residing in the vasculature and stromal regions of subcutaneous and visceral depots, are responsible for the expansion and maintenance of organ function, and are now recognised as key mediators of pathological transformation. Impaired tissue expansion drives inflammation, dysregulation of endocrine function and the deposition of lipids in the liver, muscle and around vital organs, where it is toxic. Contrary to previous hypotheses, it is the promotion of healthy adipose tissue expansion and function, not inhibition of adipogenesis, that presents the most attractive therapeutic strategy in the treatment of metabolic disease. AMP-activated protein kinase, a master regulator of energy homeostasis, has been regarded as one such target, due to its central role in adipose tissue lipid metabolism, and its apparent inhibition of adipogenesis. However, recent studies utilising AMP-activated protein kinase (AMPK)-specific compounds highlight a more subtle, time-dependent role for AMPK in the process of adipogenesis, and in a previously unexplored repression of leptin, independent of adipocyte maturity. In this article, I discuss historic evidence for AMPK-mediated adipogenesis inhibition and the multi-faceted roles for AMPK in adipose tissue.

Characterization of the Bioavailability of Per- and Polyfluoroalkyl Substances in Farmland Soils and the Factors Impacting Their Translocation to Edible Plant Tissues.

In this study, various crops and farmland soils were collected from the Fen-Wei Plain, China, to investigate the bioavailability of perfluoroalkyl substances (PFAS), their accumulation in edible plant tissues, and the factors impacting their accumulation. PFAS were frequently detected in all of the crops, with total concentrations ranging from 0.61 to 35.8 ng/g. The results of sequential extractions with water, basic methanol, and acidic methanol indicate that water extraction enables to characterize the bioavailability of PFAS in soil to edible plant tissues more accurately, especially for the shorter-chain homologues. The bioavailability of PFAS was remarkably enhanced in the rhizosphere (RS) soil, with the strongest effect observed for leafy vegetables. The water-extracted Σ16PFAS in RS soil was strongly correlated with the content of dissolved organic carbon in the soil. Tannins and lignin, identified as the main components of plant root exudates by Fourier transform-ion cyclotron resonance mass spectrometry, were found to enhance the bioavailability of PFAS significantly. Redundancy analysis provided strong evidence that the lipid and protein contents in edible plant tissues play important roles in the accumulation of short- and long-chain PFAS, respectively. Additionally, the high water demand of these tissues during the growth stage greatly facilitated the translocation of PFAS, particularly for the short-chain homologues and perfluorooctanoic acid.