Mean Diameter Of Adipocytes Research Articles

Qi Gong Wan ameliorates adipocyte hypertrophy and inflammation in adipose tissue in a PCOS mouse model through the Nrf2/HO-1/Cyp1b1 pathway: Integrating network pharmacology and experimental validation in vivo

Ethnopharmacological relevanceInitially recorded in Yifang Jijie (an ancient Chinese text), Qi Gong Wan (QGW) is used to treat obese women with infertility. QGW can help promote follicular development and maturation, regulate the balance of serum hormones between testosterone and estradiol, enhance endometrial receptivity, improve waist circumference, and ameliorate insulin resistance. It contains eight herbs: Pinellia ternata (Thunb.) Makino (Banxia), Citrus maxima (Burm.) (Juhong), Poria cocos (Schw.) Wolf. (Fuling), Atractylodes macrocephala Koidz (Baizhu), Cyperus rotundus L. (Xiangfu), Conioselinum anthriscoides 'Chuanxiong' (Chuanxiong), Massa Medicata Fermentata (Shenqu), and Glycyrrhiza uralensis Fisch. ex DC. (Gancao). However, the underlying mechanism of how QGW affects women with PCOS remains unclear.Aim of the study: QGW has been widely used to treat PCOS patients with obesity clinically. This study was designed to identify its chemical and pharmacological properties. Materials and methodsNetwork pharmacology was used to predict the active compounds, potential targets, and pathways of QGW. Female C57BL/6J mice were injected with letrozole and fed a high-fat diet to establish a PCOS-insulin resistance (PCOS-IR) model. Body weight, estrous cycles, ovarian pathology, and serum insulin resistance were measured. qRT-PCR was used to examine the inflammation-related and steroid hormone biosynthesis-related mRNA expression in adipose tissue. Western blotting was used to determine the protein levels of Nrf2, HO-1, and Cyp1b1 in adipose tissue. Molecular docking was used to reveal the key chemical compounds of QGW. ResultsNetwork pharmacology revealed a total of 91 active ingredients in QGW that were associated with 167 targets. QGW could potentially treat PCOS-IR via nitrogen metabolism, steroid hormone biosynthesis, and ovarian steroidogenesis pathways. In the PCOS-IR mouse model, we found that QGW decreased the mean diameter of adipocytes and the total adipocyte area. Furthermore, QGW was found to significantly lower the expression of inflammation-related genes including Tnfɑ and C4a/b and the steroid hormone biosynthesis-related gene Cyp1b1. QGW showed a tendency to improve cystic follicles, fasting insulin, and HOMA-IR index in the PCOS-IR mouse model. Combining these findings with the results of KEGG analysis, we conclude that QGW promotes the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue under conditions of PCOS. Molecular docking revealed that rutin, nicotiflorin, and baicalein may be the key chemical compounds of QGW through which it improves adipocyte hypertrophy and inflammation. ConclusionsQGW improved adipocyte hypertrophy and inflammation in the PCOS-IR mouse model by activating the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue. Our work thus provides a new research avenue for the study of traditional Chinese medicine in the treatment of PCOS.

Lemon Balm and Corn Silk Extracts Mitigate High-Fat Diet-Induced Obesity in Mice.

Lemon balm and corn silk are valuable medicinal herbs, which exhibit variety of beneficial effects for human health. The present study explored the anti-obesity effects of a mixture of lemon balm and corn silk extracts (M-LB/CS) by comparison with the effects of single herbal extracts in high-fat diet (HFD)-induced obesity in mice. HFD supplementation for 84 days increased the body weight, the fat mass density, the mean diameter of adipocytes, and the thickness of fat pads. However, oral administration of M-LB/CS significantly alleviated the HFD-mediated weight gain and adipocyte hypertrophy without affecting food consumption. Of the various combination ratios of M-LB/CS tested, the magnitude of the decreases in weight gain and adipocyte hypertrophy by administration of 1:1, 1:2, 2:1, and 4:1 (w/w) M-LB/CS was more potent than that by single herbal extracts alone. In addition, M-LB/CS reduced the HFD-mediated increases in serum cholesterol, triglyceride, and low-density lipoprotein, prevented the reduction in serum high-density lipoprotein, and facilitated fecal excretion of cholesterol and triglyceride. Moreover, M-LB/CS mitigated the abnormal changes in specific mRNAs associated with lipogenesis and lipolysis in the adipose tissue. Furthermore, M-LB/CS reduced lipid peroxidation by inhibiting the HFD-mediated reduction in glutathione, catalase, and superoxide dismutase. Therefore, M-LB/CS is a promising herbal mixture for preventing obesity.

Circulating Wnt1-inducible signaling pathway protein-1 (WISP-1/CCN4) is a novel biomarker of adiposity in subjects with type 2 diabetes.

Wnt1-inducible signaling pathway protein 1, or cellular communication network factor 4 (CCN4), a member of CCN family of secreted, extracellular matrix associated signaling proteins, recently was validated as a novel adipose tissue derived cytokine. To assess the relationships between circulating CCN4, adipose tissue distribution and function, and chronic low-grade inflammation in subjects with type 2 diabetes. We observed 156 patients with type 2 diabetes and 24 healthy controls. Serum levels of CCN4, hsCRP and alpha1-acid glycoprotein (alpha1-AGP) were measured by ELISA. Serum concentrations of leptin, resistin, visfatin, adipsin, adiponectin, IL-6, IL-8, IL-18 and TNF-alpha were determined by multiplex analysis. Fat mass and distribution was assessed by DEXA. Mean diameter of adipocytes was estimated in samples of subcutaneous adipose tissue. Patients with diabetes had higher levels of circulating CCN4, leptin, resistin, adipsin, visfatin, hsCRP, alpha1-AGP, and IL-6 (all p<0.02). The CCN4 concentration correlated positively with percentage of fat mass in central abdominal area, as well as with leptin, resistin and visfatin levels; negative correlation was found between CCN4 and mean adipocyte diameter. In multiple regression analysis fat mass in central abdominal area was independent predictor for CCN4 concentration. In subjects with type 2 diabetes serum levels of CCN4 are associated with central abdominal fat mass and adipose tissue dysfunction.

Upregulation of Lipocalin 2 in Adipose Tissues of Severely Obese Women: Positive Relationship With Proinflammatory Cytokines

Because the role of lipocalin 2 (LCN2) in morbid obesity is still not well defined, the aim of this study was to evaluate the circulating levels and the expression of LCN2 in visceral (VAT) and subcutaneous adipose tissue (SAT) in severely obese (SO) women. We also analyzed its relationship with inflammatory cytokines in the same subjects. The study comprised 90 white women, 39 of whom were lean controls (BMI ≤25kg/m(2)) and 51 SO (BMI ≥40kg/m(2)). Both circulating and adipose tissue levels of LCN2 were quantified by enzyme-linked immunosorbent assays. LCN2 mRNA levels from VAT and SAT were assessed by real-time reverse transcriptase-PCR (n = 60). LCN2 serum levels were significantly higher in the SO women than in the lean controls (P = 0.042), and were found to be strongly correlated with tumor necrosis factor receptor I (TNFR1) circulating levels. In the SO cohort, LCN2 serum levels were also associated with higher BMI values, but not with the homeostasis model assessments of insulin resistance (HOMA2-IR). LCN2 mRNA expression was markedly higher in SO women than in lean women in both VAT (P = 0.043) and SAT (P = 0.031). In SAT, LCN2 was negatively correlated with adiponectin and adiponectin receptor-2 expression, and positively with interleukin-6 (IL-6) expression. A strong positive correlation was also found between LCN2 expression and the mean diameter of adipocytes in VAT. Our results revealed that the circulating level of LCN2 is associated with obesity and BMI. LCN2 mRNA is over-expressed in adipose tissue from SO subjects. Finally, the expression of LCN2 is strongly related to an expression profile of proinflammatory cytokines but not to insulin resistance in nondiabetic SO women.

Quantification of pericaudal adipocyte diameter in dairy cattle during peripartum: a complementary method to study energetic status using conventional histology

The energetic status of high-yielding Holstein-Friesian dairy cattle was studied during peripartum under field conditions using body condition score (BCS), glycemia, seric ß-hydroxybutyrate and adipose tissue cellularity. This last method was tested as a complementary tool for energetic status assessment. Biopsies of pericaudal subcutaneous adipose tissue were obtained from 25 multiparous animals at 28 days before and 21 days after parturition. Samples were routinely processed for histological examination and stained with haematoxylin and eosin (H&E). The mean diameter of adipocytes (MDA) was measured with the aid of a digital image processor. During the same period, blood samples were collected weekly for metabolite determinations. The MDA at 28 days pre-partum and 21 days post-partum were 72.1 vs. 66.2 μm respectively (p = 0.055), and the corresponding BCS at these moments was 3.32 vs. 3.19 (p = 0.068). At -28 days pre-partum, the BCS was positively correlated with MDA (Pearson's r = 0.521, p = 0.016) and with glycemia (Pearson's r = 0.404, p = 0.056). Correlations between BCS and MDA, and between BCS and glycemia, with ß-hydroxybutyrate although not significant, suggest that routine histological preparations of biopsies from subcutaneous adipose tissue could be included as an easy and valuable tool for research purposes to evaluate metabolic adaptation of dairy cows to peripartum, as well as the incidence of metabolic disorders and productive performance.

Lipid droplet analysis in caveolin-deficient adipocytes: alterations in surface phospholipid composition and maturation defects

Caveolins form plasmalemnal invaginated caveolae. They also locate around intracellular lipid droplets but their role in this location remains unclear. By studying primary adipocytes that highly express caveolin-1, we characterized the impact of caveolin-1 deficiency on lipid droplet proteome and lipidome. We identified several missing proteins on the lipid droplet surface of caveolin-deficient adipocytes and showed that the caveolin-1 lipid droplet pool is organized as multi-protein complexes containing cavin-1, with similar dynamics as those found in caveolae. On the lipid side, caveolin deficiency did not qualitatively alter neutral lipids in lipid droplet, but significantly reduced the relative abundance of surface phospholipid species: phosphatidylserine and lysophospholipids. Caveolin-deficient adipocytes can form only small lipid droplets, suggesting that the caveolin-lipid droplet pool might be involved in lipid droplet size regulation. Accordingly, we show that caveolin-1 concentration on adipocyte lipid droplets positively correlated with lipid droplet size in obese rodent models and human adipocytes. Moreover, rescue experiments by caveolin- green fluorescent protein in caveolin-deficient cells exposed to fatty acid overload demonstrated that caveolin-coated lipid droplets were able to grow larger than caveolin-devoid lipid droplets. Altogether, these data demonstrate that the lipid droplet-caveolin pool impacts on phospholipid and protein surface composition of lipid droplets and suggest a functional role on lipid droplet expandability.

Anti-obese and Hypolipemic Effects of the Aqueous Extracts of Raphani Semen in Mice Fed High Fat Diet

Raphani Semen (RS) has been used to treat digestive disorders in Korean oriental medicine. The hypolipemic and anti-obese effects of the aqueous extracts of RS in mice provided with high fat diet (HFD) were evaluated. HFD caused increased T-Chol, triglyceride, and LDL, and decreased HDL levels. Mice fed HFD exhibited signs of obesity including increased body weight, fat weight, and serum leptin level, and decreased serum adiponectin level. Histopathological analysis revealed that the mean diameter of adipocytes was increased by HFD supply. However, these increases in the hyperlipemia and obesity indices were attenuated by RS treatment in a dose-dependent manner, and similar effects were detected in mice treated with equal dosages (250 mg/kg) of metformin and RS. These results indicate that the aqueous extracts of RS warrant further development as a protective agent for the treatment of diet-induced metabolic syndrome.

Influence of feed intake during pregnancy and lactation on fat body reserve mobilisation, plasma leptin and reproductive function of primiparous lactating sows.

From day 23 of pregnancy, 24 gilts received either a medium (M, n = 16) or a high (H, n = 8) level of feeding calculated to meet 115% or 190% of energy for maintenance, respectively. During lactation, all H sows were fed ad libitum (H-AL) whereas M sows were fed either ad libitum (M-AL, n = 8) or were restricted (M-RE, n = 8) to the amount of feed ingested by H-AL sows. Increased feed intake during pregnancy increased live weight, backfat thickness, and estimated body lipid and protein on days 4 and 25 of lactation (P < 0.05). It also resulted in lower feed intake and higher lipid mobilisation during lactation (P < 0.05) without a detrimental influence on milk production. Activities of malic enzyme and glucose-6-phosphate dehydrogenase from neck fat samples were higher in H than M sows on day 4 (P < 0.05). They decreased during lactation in H sows (P < 0.05). Mean diameter of adipocytes decreased during lactation in the 3 groups (P < 0.05) but did not differ between groups on days 4 and 25. Plasma leptin on days 4, 11, 18 and 25 was higher in H than in M sows (P < 0.05) but was not influenced by lactational feed intake. Neither measured characteristics of gonadotrophin secretion on day 22, nor of ovarian activity on day 26, were significantly influenced by the level of feeding during pregnancy or lactation.

Comparison of fatty acid composition among isolated bovine adipocytes with different sizes

SummaryThe relationship between the diameter of adipocytes distributed in the same piece of subcutaneous adipose tissue and main fatty acid composition from fattening Holstein steers was investigated. A preliminary experiment was carried out to investigate whether the isolation process of adipocytes caused any change in the main fatty acid composition. It was shown that there was little difference in the main fatty acid composition of adipose tissue (X) and that of adipocytes (Y) isolated by this method. The regression equation was: Y = 0.97X + 0.47, R2 = 0.99 (p &lt; 0.01). Adipocytes were isolated from Holstein steers at the early and late fattening stages and then separated into two fractions by using a mesh with a pore size of 50 µm. In adipocytes from Holstein steers at the late fattening stage, the large adipocytes with a mean diameter of 117.5 µm contained more (p &lt; 0.01) myristoleic acid (14:1), palmitoleic acid (16:1) and oleic acid (18:1), and less (p &lt; 0.01) palmitic acid (16:0) and stearic acid (18:0) than the small adipocytes with a mean diameter of 28.7 µm. Similar results have been shown in adipocytes from Holstein steers at the early fattening stages. The isolated adipocytes from finishing Holstein steers were separated into four fractions by using meshes with pore size of 25, 50, 75 and 100 µm. The mean diameter of adipocytes in fractions 1, 2, 3 and 4 were 35.2, 80.5, 113.7 and 141.7 µm, respectively. With increasing adipocyte size, the rates of myristoleic acid (14:1) and palmitoleic acid (16:1) increased (the correlation coefficients were 0.93, p &lt; 0.01 and 0.86, p &lt; 0.01, respectively), whereas that of palmitic acid (16:0) and stearic acid (18:0) decreased (the correlation coefficients were ‐0.44 and ‐0.80, p &lt; 0.01, respectively). It is suggested that the size of adipocyte is one of the important determinants of fatty acid composition in subcutaneous adipocytes of Holstein steers.

ホルスタイン種去勢肥育牛の皮下脂肪細胞の大きさと脂肪酸組成との関連

The fatty acid composition and the diameter of subcutaneous adipocytes from 13 Holstein steers at different fattening stages were investigated. The mean diameter of adipocytes from individual steers was positively (P<0.01) correlated with the percentage of myristoleic acid (14:1)(r=0.91), palmitoleic acid (16:1)(r=0.83) or oleic acid (18:1)(r=0.82), and negatively(P<0.01)correlated with the percentage of stearic acid (18:0)(r=-0.89). The isolated adipocytes from the same finishing steer (n=5)were then separated by a 50μm mesh. The large adipocytes which remained on the mesh (118μm mean diameter)contained more (P<0.01) myristoleic acid (14:1)palmitoleic acid (16:1) and oleic acid (18:1), and less (P<0.01) palmitic acid(16:0), stearic acid (18:0) than the small adipocytes which were filtered through (29μm mean diameter). It is suggested that the growth of adipocyte is one of the important determinants of fatty acid composition in subcutaneous adipocytes of Holstein steers throughout the fattening period.

Increased insulin suppression of plasma free fatty acid concentration in exercise-trained rats.

The effect of exercise training on the insulin suppression of plasma free fatty acid (FFA) concentrations was studied in unanesthetized rats with the hyperinsulinemic-euglycemic clamp technique. Seven rats trained (TR) for 3 h/day by continuous swimming during 8 wk were compared with 6 untrained (UT) body weight-matched rats. Both TR and UT rats were submitted to an exercise swimming session 18 h before the clamp. A smaller mean diameter of adipocytes sampled from the epididymal fat depot was measured in TR animals. The total quantity of glucose infused to maintain euglycemia was 2.2 times higher in TR than in UT animals. No significant differences in plasma insulin concentrations were found between the two groups throughout the experiment. Insulin infusions resulted in a 60% decrease of plasma FFA in TR rats (mean value: from 0.46 to 0.18 mM) compared with 27% in UT animals (mean value: from 0.45 to 0.33 mM). The data indicate a greater ability of insulin to suppress plasma FFA levels with exercise training, which suggests an increased antilipolytic action of insulin in adipocytes under this condition.

Congenitally impaired hormone sensitivity of the adipose tissue of spontaneously diabetic mice, KK

Adipose tissue of KK mice was less sensitive to insulin in its stimulatory action on glucose oxidation or its inhibitory action on lipolysis, and to epinephrine in its stimulatory action on lipolysis as compared to that of C57BL mice. A lack of appreciable increase in plasma NEFA in response to fasting of the KK mice might be caused by the impaired response of lipolysis to the hormones. — Adipose tissue of KK mice was also less sensitive to insulin-like action of concanavalin A, ouabaine or omission of K+ in the medium on glucose oxidation or lipolysis. Lipolysis in response to theophylline and/or DcAMP was less marked in the tissue of KK mice. The mean diameter of the adipocytes was larger in KK than in C57BL mice. In the experiments using adipocytes with the same diameter, however, the cells of KK mice were less sensitive to the hormones than those of C57BL. — With respect to tissue sensitivity to the hormones, the mean diameter of adipocytes and the response of plasma NEFA to fasting, the F1-hybrid mice of KK and C57BL showed values between those of the parental strains. Yellow hybrid (genetically obese F1-hybrid) mice showed higher sensitivity to insulin in the adipose tissue, more remarkable response of plasma NEFA to fasting as compared with KK mice, although hypertrophy of adipocytes was more pronounced in the yellow hybrid mice. — These findings suggest that insulin insensitivity is associated with epinephrine insensitivity in adipocytes of KK mice; both appear to be subjected to genetic factor(s)per se rather than hypertrophy of the adipocytes. Furthermore, insensitivity to both hormones in the KK mice appears to be caused by a common defect in cellular process other than the hormone receptor systems. These genetically determined abnormalities of adipocytes may result in fat-storage metabolism through hyperinsulinemia; this is very similar to the metabolic profile due to thrifty genotype in human diabetes as proposed by Neel.