Saponins from Panax japonicus alleviate adipose tissue fibrosis and metabolic dysfunction in high-fat-diet-induced obese mice.

INTRODUCTION: Adipose tissue fibrosis is a typical feature of adipose tissue dysfunction in obese individuals, which is closely related to metabolic diseases. OBJECTIVE: To explore the effect and mechanism of Saponins from Panax japonicus (SPJ) on adipose tissue fibrosis in obese mice induced by high fat diet (HFD). MATERIALS AND METHODS: We established a HFD induced obese mice model. Then the obese mice were treated with 90 mg/kg SPJ by oral gavage for 10 weeks. The levels of adipose tissue fibrosis and molecules related to signalling pathways were measured. Then the effects of SPJ on TGFß1-induced fibrosis in 3T3-L1 differentiated adipocytes were evaluated. RESULTS: SPJ reduced body weight, fat accumulation, and improved glucose and lipid metabolism in obese mice. SPJ decreased collagen deposition and expressions of fibrotic genes in epididymal white adipose tissue (eWAT) of obese mice. SPJ decreased the levels of TGFß1 protein and pSmad2, and increased the expression of PPARγ and PGC1α, thus alleviating oxidative stress in eWAT. Consistently, SPJ inhibited TGFß1-induced fibrosis in 3T3-L1 differentiated adipocytes. CONCLUSIONS: SPJ may alleviate adipose tissue fibrosis and improve obesity by inhibiting TGFß1/Smad2 and activating PPARγ/PGC1α pathway. SPJ is expected to become an efficient medicine for treatment of obesity.

Discovery of bicyclic polyprenylated acylphloroglucinols from Hypericum himalaicum with glucose transporter 4 translocation activity.

Hyperhimatins A-P (1-16), sixteen new bicyclic polyprenylated acylphloroglucinols (BPAPs), were isolated and identified from Hypericum himalaicum. The planner structures of hyperhimatins A-P were confirmed via extensive NMR and careful HRESIMS data analysis. The absolute configurations of the new compounds were mainly determined by electronic circular dichroism (ECD) calculation, NMR calculation, and the circular dichroism data of the in situ formed [Rh2(OCOCF3)4] complexes. All compounds were assessed for the glucose transporter 4 (GLUT-4) translocation and expression enhancing effects in L6 myotubes. Compounds 1-16 could promote the GLUT-4 expression by the range of 1.95-6.04 folds, and accelerate the GLUT-4 fusion with the plasma membrane ranged from 53.56% to 76.97% at a consistence of 30 µg/mL, among compound 10 displayed the strongest GLUT-4 translocation effect.

Parallel analysis of global garlic gene expression and alliin content following leaf wounding.

BACKGROUND: Allium sativum (garlic) is an economically important food source and medicinal plant rich in sulfides and other protective substances such as alliin, the precursor of allicin biosynthesis. Cysteine, serine and sulfur is the precursor of alliin biosynthesis. However, little is known about the alliin content under abiotic stress or the mechanism by which it is synthesized. RESULTS: The findings revealed that the content of alliin was lowest in the garlic roots, and highest in the buds. Furthermore, alliin levels decreased in mature leaves following wounding. Transcriptome data generated over time after wounding further revealed significant up-regulation of genes integral to the biosynthetic pathways of cysteine and serine in mature garlic leaves. CONCLUSIONS: The findings suggest that differential expression of cysteine, serine and sulfide-related genes underlies the accumulation of alliin and its precursors in garlic, providing a basis for further analyses of alliin biosynthesis.

Maternal nicotine exposure during pregnancy and lactation induces brown adipose tissue whitening in female offspring.

Maternal nicotine exposure during pregnancy and lactation is associated with obesity in female offspring. Brown adipose tissue (BAT) is related to energy metabolism and obesity. In this study, we explored the mechanism of maternal nicotine exposure on BAT "whitening" in female offspring. Pregnant rats were randomly assigned to nicotine (1.0 mg/kg twice per day, subcutaneous administration) or control groups. The weight, structure, and microvascular density of interscapular BAT (iBAT) and the expression of PGC-1αUCP1 signals, mitochondrial biogenesis-related genes and angiogenesis-related genes were tested in 4- and 26-week-aged female offspring. In vitro, C3H10T1/2 cells were induced to differentiate into mature brown adipocytes, and 0-50 µM nicotine was treated on cells during the differentiation process. Nicotine-exposed females had higher iBAT weight, white-like adipocytes and abnormal mitochondrial structure in iBAT at 26 weeks rather than 4 weeks. The PGC-1αUCP1 signals and brown-like genes were down-regulated at 26 weeks, but the microvascular density and the expression of pro-angiogenic factors reduced more at 4 weeks in the nicotine group. In vitro, 50 µM nicotine significantly decreased the expression of PGC-1αUCP1 signals and angiogenesis-related genes. In conclusion, maternal nicotine exposure during pregnancy and lactation led to the "whitening" of BAT in adult female offspring: nicotine decreased BAT angiogenesis in the early development stage, and then, the impairment of blood vessels programed for the reduction of BAT phenotype through down-regulating the PGC-1αUCP1 signals in adulthood. This impairment of BAT may be a potential mechanism of nicotine-induced obesity in female offspring.

A composition of ursolic acid derivatives from Ludwigia hyssopifolia induces apoptosis in throat cancer cells via the Akt/mTOR and mitochondrial signaling pathways and by modulating endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Ludwigia hyssopifolia (LH), an ethnopharmacological herb used in Guangxi Zhuang medicine, is known for its extensive therapeutic use in treating throat disorders. The anti-laryngeal-cancer benefits of the ethyl acetate and petroleum ether fractions of the ethanolic extracts of LH have been shown in our prior cell-based research. Nevertheless, the specific impacts and underlying processes by which LH combats throat cancer effects have not been fully understood. AIM OF THE STUDY: This study involved the extraction of a composition containing two derivatives of ursolic acid from LH (LH-CUAD). The present study aimed to assess the anti-throat-cancer effects of these derivatives and the underlying mechanisms through in vitro and in vivo experiments. MATERIALS AND METHODS: Solvent extraction, fractionation, chromatography, and semipreparative high-performance liquid chromatography were used for the extraction, purification, and analysis of LH-CUAD. The in vitro and in vivo anti-throat-cancer effects of LH-CUAD were investigated using the throat cancer cell lines Hep-2 and FaDu as well as Hep-2 tumor-bearing nude mice. RESULTS: LH-CUAD significantly inhibited the proliferation and migration of throat cancer cells without any prominent toxicity. The Hoechst 33258 staining, Annexin V-FITC/PI double-staining assays, and flow cytometry confirmed that LH-CUAD could induce throat cancer cell death from early to late apoptosis in vitro. LH-CUAD exhibited significant antitumor activity and low toxicity in a xenograft model, and induced throat cancer cells apoptosis in vivo. The apoptotic effects of LH-CUAD therapy were validated using Western blotting, which demonstrated the activation of a caspase cascade response triggered by an imbalance between the endoplasmic reticulum and mitochondria. In addition, it was observed that LH-CUAD exhibited inhibitory effects on Akt and mTOR phosphorylation, hence promoting apoptosis. CONCLUSIONS: LH-CUAD induces apoptosis in both in vivo and in vitro models of throat cancer. This effect is achieved by activating the mitochondrial pathway, inhibiting the Akt/mTOR pathway and initiating endoplasmic reticulum stress. The findings of this study suggest that LH-CUAD has the potential to offer a novel approach to the clinical management of throat cancer.

Adipocyte-specific FAK deletion promotes pancreatic ß-cell apoptosis via adipose inflammatory response to exacerbate diabetes mellitus.

BACKGROUND: White adipose tissue (WAT) has a key role in maintaining energy balance throughout the body, and their dysfunction take part in the regulation of diabetes mellitus. However, the internal regulatory mechanisms underlying are still unknown. METHODS AND RESULTS: We generated adipocyte-specific FAK KO (FAK-AKO) mice and investigated their phenotype. The cascade of adipocyte, macrophage in adipocyte tissues, and pancreatic ß-cells were proposed in FAK-AKO mice and validated by cell line studies using 3T3-L1, Raw264.7 and Min6. The FAK-AKO mice exhibited glucose intolerance, reduced adipose tissue mass and increased apoptosis, lipolysis and inflammatory response in adipose tissue. We further demonstrate that adipocyte FAK deletion increases ß cell apoptosis and inflammatory infiltrates into islets, which is potentiated if mice were treated with STZ. In the STZ-induced diabetes model, FAK AKO mice exhibit less serum insulin content and pancreatic ß cell area. Moreover, serum pro-inflammatory factors increased and insulin levels decreased after glucose stimulation in FAK AKO mice. In a parallel vitro experiment, knockdown or inhibition of FAK during differentiation also increased apoptosis, lipolysis and inflammatory in 3T3-L1 adipocytes, whereas the opposite was observed upon overexpression of FAK. Moreover, coculturing LPS-treated RAW264.7 macrophages with knockdown FAK of 3T3-L1 adipocytes increased macrophage pro-inflammatory response. Furthermore, conditioned medium from above stimulated Min6 cells apoptosis (with or without STZ), whereas the opposite was observed upon overexpression of FAK. Mechanistically, FAK protein interact with TRAF6 in adipocytes and knockdown or inhibition of FAK activated TRAF6/TAK1/NF-κB signaling, which exacerbates inflammation of adipocytes themselves. CONCLUSION: Adipocyte FAK deletion promotes both adipocyte apoptosis and adipose tissue inflammation. Pro-inflammatory factors released by the FAK-null adipose tissue further trigger apoptosis in pancreatic islets induced by the administration of STZ, thereby exacerbating the diabetes mellitus. This study reveals a link between FAK-mediated adipose inflammation and diabetes mellitus, a mechanism that has not been previously recognized.

Reweighted multi-view clustering with tissue-like P system.

Multi-view clustering has received substantial research because of its ability to discover heterogeneous information in the data. The weight distribution of each view of data has always been difficult problem in multi-view clustering. In order to solve this problem and improve computational efficiency at the same time, in this paper, Reweighted multi-view clustering with tissue-like P system (RMVCP) algorithm is proposed. RMVCP performs a two-step operation on data. Firstly, each similarity matrix is constructed by self-representation method, and each view is fused to obtain a unified similarity matrix and the updated similarity matrix of each view. Subsequently, the updated similarity matrix of each view obtained in the first step is taken as the input, and then the view fusion operation is carried out to obtain the final similarity matrix. At the same time, Constrained Laplacian Rank (CLR) is applied to the final matrix, so that the clustering result is directly obtained without additional clustering steps. In addition, in order to improve the computational efficiency of the RMVCP algorithm, the algorithm is embedded in the framework of the tissue-like P system, and the computational efficiency can be improved through the computational parallelism of the tissue-like P system. Finally, experiments verify that the effectiveness of the RMVCP algorithm is better than existing state-of-the-art algorithms.

Adipose extracellular matrix deposition is an indicator of obesity and metabolic disorders.

Obesity and metabolic disorders are threats to human health. Extracellular matrix (ECM) is an important member of adipose microenvironment. ECM remodeling contributes to obesity and insulin resistance, but the roles of every single ECM component is still not fully understood. We observed glucose and lipids metabolic disorders in high-fat diet (HFD)-fed mice and humans with obesity. Higher levels of inflammatory factors and hormones existed in serum of HFD-fed mice. Multiple collagens, laminins, fibronectin, nidogen, and Hspg2 were upregulated in obese white adipose tissue (WAT) from mice and humans. These effects were stronger in subcutaneous WAT than visceral WAT in mice, but the fat depot difference was reversed in humans. The ECM structure and the morphology of adipocytes seeded on ECM were changed in the HFD group. In human visceral WAT, ECM genes showed positive correlations with blood lipids and glucose. In vitro, collagen I/IV and LAMA4 proteins showed similar changes with C/EBPα during the differentiation of adipocytes. Macromolecular crowders (MMC) promoted partial collagen and non-collagen gene expression. Oleic acid (OA) and MMC upregulated collagen I/IV and LAMA4 proteins, and the effects of MMC were stronger than that of OA. Moreover, MMC promoted the differentiation of adipocytes, but OA increased the size of lipid droplets. Positive correlations were observed between ECM genes and adipogenesis-related genes in adipocytes. In conclusion, some obesogens (such as HFD) induce ECM remodeling, and the upregulation of ECM components is closely related to adipogenesis, suggesting that adipose ECM deposition is an indicator of obesity and metabolic disorders.

Mulberry extract ameliorates T2DM-related symptoms via AMPK pathway in STZ-HFD-induced C57BL/6J mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry (Morus alba L.) is not only a tasty food but also a beneficial medicinal substance that has been historically used to treat diabetes, as recorded in Tang Ben Cao. Recent research on animal models has shown that the ethyl acetate extract of Morus alba L. fruits (EMF) has hypoglycemic and hypolipidemic properties. However, there is a lack of documentation on the specific mechanisms through which EMF exerts its hypoglycemic effects. OBJECTIVE OF THE STUDY: This study aimed to investigate the impact of EMF on L6 cells and C57/BL6J mice and to elucidate the potential mechanisms underlying its effects. The findings of this study can contribute to the existing evidence for the application of EMF as a therapeutic drug or dietary supplement in the management of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The UPLC-Q-TOF-MS technique was utilized to gather MS data. Masslynx 4.1 software in conjunction with the SciFinder database and other relevant references were used to analyze and identify the chemical composition of EMF. A series of in vitro investigations including MTT assay, glucose uptake assay and Western blot analysis were performed using an L6 cell model stably expressing IRAP-mOrange after EMF treatment. In vivo investigations were performed on a STZ-HFD co-induced T2DM mouse model, which included assessments of body composition, biochemical tests, histopathological analysis, and Western blot analysis. RESULTS: MTT results revealed that EMF had no toxic effects on the cells at various concentrations. When EMF was administered to L6 cells, there was an increase in glucose transporter type 4 (GLUT4) translocation activity and a significant dose-dependent enhancement of glucose uptake by L6 myotubes. EMF treatment led to a marked increase in P-AMPK levels and GLUT4 expression in the cells, but these effects were reversed by an AMPK inhibitor (Compound C). In diabetic mice with STZ-HFD-induced diabetes, EMF treatment improved oral glucose tolerance, hyperglycemia, and hyperinsulinemia. Furthermore, EMF supplementation significantly reduced insulin resistance (IR) in diabetic mice, as evaluated using a steady-state model of the insulin resistance index. Histopathological sections demonstrated that acute EMF treatment reduced hepatic steatosis, pancreatic damage, and adipocyte hypertrophy. Western blot analysis demonstrated that EMF treatment also reduced abnormally high PPARγ expression, elevated the level of p-AMPK and p-ACC, and augmented the abundance of GLUT4 in insulin-sensitive peripheral tissues. SUMMARY: The results suggest that EMF may exert beneficial effects on T2DM through the AMPK/GLUT4 and AMPK/ACC pathways, as well as by regulating PPARγ expression.

An improved multi-view spectral clustering based on tissue-like P systems.

Multi-view spectral clustering is one of the multi-view clustering methods widely studied by numerous scholars. The first step of multi-view spectral clustering is to construct the similarity matrix of each view. Consequently, the clustering performance will be greatly affected by the quality of the similarity matrix of each view. To solve this problem well, an improved multi-view spectral clustering based on tissue-like P systems is proposed in this paper. The optimal per-view similarity matrix is generated in an iterative manner. In addition, spectral clustering is combined with the symmetric nonnegative matrix factorization method to directly output the clustering results to avoid the secondary operation, such as k-means or spectral rotation. Furthermore, improved multi-view spectral clustering is integrated with the tissue-like P system to enhance the computational efficiency of the multi-view clustering algorithm. Extensive experiments verify the effectiveness of this algorithm over other state-of-the-art algorithms.

High-Fat-Diet-Induced Extracellular Matrix Deposition Regulates Integrin-FAK Signals in Adipose Tissue to Promote Obesity.

SCOPE: High-fat-diet (HFD) is an important factor in obesity. Extracellular matrix (ECM) regulates white adipose tissue (WAT), but its mechanism is unknown. METHODS AND RESULTS: This study uses three models-HFD-fed mice, human with obesity, and 3T3-L1 adipocytes with oleic acid (OA)/macromolecular crowders (MMC) treatment. Glucose and lipids metabolic disorders, increased collagen I/IV and laminin α2/4 (LAMA2/4), and upregulated integrins (ITGA1/ITGA7) - focal adhesion kinase (FAK) - c-Jun N-terminal kinase (JNK)/extracellular regulated protein kinase 1/2 (ERK1/2) signals in obese WAT from mice and human are observed. The upregulation of ECM - integrin - FAK signals is stronger in subcutaneous WAT than that in visceral WAT of mice, but these results are reversed in human. In vitro, oleic acid (OA) promotes lipid accumulation and upregulates collagen IV, LAMA4, and p-JNK. MMC is used to induce ECM deposition in adipocytes. MMC promotes adipocyte differentiation and integrins - FAK - JNK/ERK1/2 signals. When FAK phosphorylation is inhibited, downstream p-JNK is decreased. Inhibition of FAK phosphorylation reduces adipocyte differentiation, but MMC partially reverses this effect. CONCLUSION: HFD-induced ECM deposition, whose signals are transmitted into adipocytes through upregulating ITGA1/ITGA7, activates the phosphorylation of intracellular FAK - JNK/ERK1/2 signals, and promotes adipogenesis in WAT. This mechanism provides novel therapeutic targets to treat obesity.

Ursolic acid induces white adipose tissue beiging in high-fat-diet obese male mice.

Ursolic acid (UA) shows an effect on obesity and related metabolic diseases, but its mechanism of action remains unclear. We found that UA clearly reduced the body weight and adipose tissue mass and improved the glucose tolerance and insulin sensitivity in obese male mice. UA treatment significantly reduced the volume and weights of the epididymal white adipose tissue (eWAT) and inguinal subcutaneous white adipose tissue (igSWAT) of HFD-fed mice, respectively. UA also decreased the expression of genes involved in adipocyte differentiation and lipogenesis in igSWAT. Real-time PCR and immunohistochemistry showed that the expression of beiging-related genes 4-1BB factor (CD137), T-box transcription factor 1 (TBX1), and transmembrane protein 26 (TMEM26) were significantly increased in the UA treatment group. UA treatment significantly reduced the weight of gastrocnemius muscle (GM) and lipid droplets in the GM. UA treatment significantly upregulated the expression of PR domain-containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and fibronectin type 3 domain-containing protein 5 (FNDC5) in GM and igSWAT. UA also stimulated irisin secretion in the serum. In conclusion, these results indicate that UA plays an anti-obesogenic role by increasing the secretion of irisin and promoting the beiging of WAT.

Maternal nicotine exposure impairs brown adipose tissue via AMPK-SIRT1-PGC-1α signals in male offspring.

AIMS: Maternal nicotine exposure during pregnancy and lactation is associated with obesity in offspring. Brown adipose tissue (BAT) is correlated with energy metabolism and obesity. In this study, we explored the mechanism of maternal nicotine exposure on BAT changes in male offspring. MAIN METHODS: Pregnant rats were randomly assigned to nicotine (1.0 mg/kg twice per day, subcutaneous administration) or control groups. In vitro, C3H10T1/2 cells were induced to differentiate into mature brown adipocytes, and 0-50 µM nicotine was given to C3H10T1/2 cells during the differentiation process. KEY FINDINGS: Nicotine-exposed males had white-like adipocytes and abnormal mitochondria structure in iBAT at 26 weeks. The expression of mitochondrial genes, UCP1 and AMPK-SIRT1-PGC-1α pathway were downregulated in the nicotine group at 26 weeks rather than 4 weeks. In vitro, 50 µM nicotine decreased the expression of mitochondrial genes, UCP1 and AMPK-SIRT1-PGC-1α pathway in brown adipocytes. SIGNIFICANCE: Maternal nicotine exposure showed the "programming" effect on the decreased brown-like phenotype in BAT of adult male offspring via downregulating AMPK-SIRT1-PGC-1α pathway. This impairment of BAT may be a potential mechanism of nicotine-induced obesity in male offspring.

Maternal nicotine exposure enhances adipose tissue angiogenic activity in offspring: Sex and age differences.

Maternal nicotine exposure during pregnancy and lactation (NIC) is associated with dysfunction of white adipose tissue (WAT). We focused on the NIC-induced WAT angiogenesis and explored its sex and age differences. Pregnant rats were randomly assigned to NIC (1.0 mg/kg nicotine twice per day) or control groups. Distribution and density of blood vessels were observed. Angiogenesis-related genes were tested at 4, 12 and 26 weeks to estimate angiogenic activity. In vitro, nicotine concentration- and time-response experiments (0-50 µM) were conducted in 3T3-L1. Lipid accumulation and angiogenesis-related genes were tested. NIC increased the blood vessels in inguinal subcutaneous WAT (igSWAT) and gonadal WAT (gWAT) of 26-week-aged male and 4-week-aged female offspring. In males, nicotine showed higher angiogenic activity at 26 weeks than at 4 weeks in igSWAT and gWAT. In females, nicotine's angiogenic activity was higher at 4 weeks than 26 weeks in igSWAT and gWAT. In vitro, nicotine promoted adipocyte differentiation, and increased the expression of angiogenesis-related genes in concentration- and time dependent manners. In conclusion, NIC-induced enhancement of angiogenic activity in WAT presented sex and age differences: nicotine showed higher angiogenic activity in adulthood than in childhood of male offspring, but the converse results were observed in female offspring.

The association between maternal nicotine exposure and adipose angiogenesis in female rat offspring: A mechanism of adipose tissue function changes.

Maternal smoking during pregnancy and lactation is associated with increased fat mass in the offspring, but the mechanism by which this occurs is not fully understood. Our study focused on the relationships among maternal nicotine exposure, adipose angiogenesis and adipose tissue function in female offspring. Pregnant rats were randomly assigned to nicotine or control groups. Microvascular density, lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested in 4-, 12- and 26-week female offspring. In vitro, nicotine concentration- and time-response experiments were conducted in 3T3-L1. Lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested. The conditioned media of differentiated 3T3-L1 treated with nicotine were used to observe tube formation in human umbilical vein endothelial cells (HUVECs). Nicotine-exposed females presented higher adipose microvascular density. The gene expression of α7nAChR, Egr1 and FGF2 was significantly increased in gonadal white adipose tissue (gWAT) and inguinal subcutaneous WAT (igSWAT) of nicotine-exposed females at 4 weeks of age. The protein expression of α7nAChR, Egr1 and FGF2 was increased in gWAT and igSWAT of nicotine-exposed females at 4 weeks of age, and increased in gWAT at 26 weeks. In vitro, nicotine increased the expression of lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins in a concentration- and time-dependent manner. In the tube formation experiment, adipocytes affected by nicotine promoted HUVEC angiogenesis. Therefore, maternal nicotine exposure promoted the early angiogenesis of adipose tissue via the α7nAChR-Egr1-FGF2 signaling pathway, and this angiogenesis mechanism was associated with increased adipogenesis in adipose tissue of female offspring.

Age Differences in the Relationship between Secondhand Smoke Exposure and Risk of Metabolic Syndrome: A Meta-Analysis.

Secondhand smoke (SHS), a common environmental exposure factor, has become a serious public health problem. Metabolic syndrome is another worldwide clinical challenge. Our study tried to determine the age differences in the relationship between SHS and the risk of metabolic syndrome. Studies were searched in PubMed and Web of Science from 11 November to 30 November 2018. Eighteen studies were finally included based on inclusion and exclusion criteria. The relationship between SHS and the risk indicators of metabolic syndrome was analyzed. The weighted mean difference (WMD) of fasting plasma glucose (FPG), insulin, body mass index (BMI), and waist circumference (WC), and the standard mean difference (SMD) of total cholesterol, triglycerides, and low- and high-density lipoprotein-cholesterol (LDL-C, HDL-C) were calculated in a meta-analysis. SHS was positively associated with the level of insulin and WC. According to the subgroup analysis based on age difference, SHS was positively associated with FPG in the upper age group, and positively associated with LDL-C and negatively associated with HDL-C in the lower age group. BMI showed a more obvious positive correlation in the adults group than in the children and the teenagers group. In conclusion, the association of metabolic syndrome with SHS varies with age. When exposed to SHS, older people may be more susceptible to glucose metabolic disorder, but younger people may be more susceptible to lipid metabolic disorder.

Effects of maternal omega-3 fatty acids supplementation during pregnancy/lactation on body composition of the offspring: A systematic review and meta-analysis.

BACKGROUND & AIMS: The effect of maternal omega-3 fatty acids intake on the body composition of the offspring is unclear. The aim of this study was to conduct a systematic review and meta-analysis to confirm the effects of omega-3 fatty acids supplementation during pregnancy and/or lactation on body weight, body length, body mass index (BMI), waist circumference, fat mass and sum of skinfold thicknesses of offspring. METHODS: Human intervention studies were selected by a systematic search of PubMed, Web of Science, the Cochrane Library and references of related reviews and studies. Randomized controlled trials of maternal omega-3 fatty acids intake during pregnancy or lactation for offspring's growth were included. The data were analyzed with RevMan 5.3 and Stata 12.0. Effect sizes were presented as weighted mean differences (WMD) or standardized mean difference (SMD) with 95% confidence intervals (95% CI). RESULTS: Twenty-six studies comprising 10,970 participants were included. Significant increases were found in birth weight (WMD = 42.55 g, 95% CI: 21.25, 63.85) and waist circumference (WMD = 0.35 cm, 95% CI: 0.04, 0.67) in the omega-3 fatty acids group. There were no effects on birth length (WMD = 0.09 cm, 95% CI: -0.03, 0.21), postnatal length (WMD = 0.13 cm, 95% CI: -0.11, 0.36), postnatal weight (WMD = 0.04 kg, 95% CI: -0.07, 0.14), BMI (WMD = 0.09, 95% CI: -0.05, 0.23), the sum of skinfold thicknesses (WMD = 0.45 mm, 95% CI: -0.30, 1.20), fat mass (WMD = 0.05 kg, 95% CI: -0.01, 0.11) and the percentage of body fat (WMD = 0.04%, 95% CI: -0.38, 0.46). CONCLUSIONS: This meta-analysis showed that maternal omega-3 fatty acids supplementation can increase offspring's birth weight and postnatal waist circumference. However, it did not appear to influence children's birth length, postnatal weight/length, BMI, sum of skinfold thicknesses, fat mass and the percentage of body fat during postnatal period. Larger, well-designed studies are recommended to confirm this conclusion.

Perinatal nicotine exposure increases obesity susceptibility by peripheral leptin resistance in adult female rat offspring.

Maternal nicotine (NIC) exposure causes overweight, hyperleptinemia and metabolic disorders in adult offspring. Our study aims to explore the underlying mechanism of perinatal NIC exposure increases obesity susceptibility in adult female rat offspring. In our model, we found that adult NIC-exposed females presented higher body weight and subcutaneous and visceral fat mass, as well as larger adipocytes, while no change was found in food intake. Serum profile showed a higher serum glucose, insulin and leptin levels in NIC-exposed females. In adipose tissue and liver, the leptin signaling pathway was blocked at 26 weeks, presented lower Janus tyrosine kinase 2 and signal transducer and activator of transcription 3 gene expression, higher suppressor of cytokine signaling 3 gene expression (in adipose tissue) and lower leptin receptors gene expression (in liver), indicating that peripheral leptin resistance occurred in NIC-exposed adult females. In female rats, the expression of lipolysis genes was affected dominantly in adipose tissue, but lipogenesis genes was affected in liver. Furthermore, the glucose and insulin tolerance tests showed a delayed glucose clearance and a higher area under the curve in NIC-exposed females. Therefore, perinatal NIC exposure programed female rats for adipocyte hypertrophy and obesity in adult life, through the leptin resistance in peripheral tissue.