• Molecules and Cells
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• v.41 no.10
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• pp.900-908
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• 2018

Insulin resistance is closely associated with metabolic diseases such as type 2 diabetes, dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones (TZDs) have been developed to ameliorate insulin resistance by activation of peroxisome proliferator-activated receptor (PPAR) ${\gamma}$. Although TZDs are synthetic ligands for $PPAR{\gamma}$, metabolic outcomes of each TZD are different. Moreover, there are lack of head-to-head comparative studies among TZDs in the aspect of metabolic outcomes. In this study, we analyzed the effects of three TZDs, including lobeglitazone (Lobe), rosiglitazone (Rosi), and pioglitazone (Pio) on metabolic and thermogenic regulation. In adipocytes, Lobe more potently stimulated adipogenesis and insulin-dependent glucose uptake than Rosi and Pio. In the presence of pro-inflammatory stimuli, Lobe efficiently suppressed expressions of pro-inflammatory genes in macrophages and adipocytes. In obese and diabetic db/db mice, Lobe effectively promoted insulin-stimulated glucose uptake and suppressed pro-inflammatory responses in epididymal white adipose tissue (EAT), leading to improve glucose intolerance. Compared to other two TZDs, Lobe enhanced beige adipocyte formation and thermogenic gene expression in inguinal white adipose tissue (IAT) of lean mice, which would be attributable to cold-induced thermogenesis. Collectively, these comparison data suggest that Lobe could relieve insulin resistance and enhance thermogenesis at low-concentration conditions where Rosi and Pio are less effective.

• Development and Reproduction
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• v.20 no.3
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• pp.197-205
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• 2016

Adipose tissue is one of the major endocrine gland. More recently, local production of steroids in adipocytes differentiated from mouse 3T3-L1 cell-line was reported. We hypothesized that rat adipocytes have steroidogenic machinery and the expression patterns of the components might be differentially regulated, depending on the distribution and sex. To verify this hypothesis, we collected the adipose tissues depot-and sex-specifically at postnatal day (PND) 30, and performed quantitative RT-PCRs. In overall aspects, the abundances of the transcripts were lower in the brown adipose of both sexes. $3{\beta}-HSD$ transcript levels in female abdominal and reproductive adipose, CYP17 transcript levels in female reproductive adipose, $17{\beta}-HSD$ transcript levels in female abdominal and reproductive adipose, and CYP19 transcript levels in female abdominal adipose were significantly lower than those of male counterparts. Similar to steroidogenic factors, the abundance of the $ER-{\alpha}$ transcripts were generally lower in the brown adipose of both sexes. $ER-{\beta}$ transcripts were more abundant in male white adipose depots than their female counterparts. The levels of LHR transcripts in female reproductive adipose were significantly higher than those of male counterpart. In conclusion, our study demonstrated that the expressions of steroidogenesis-related genes were depot- and sex-specifically occurred in the immature male and female rat adipose tissues. Our study suggested that the adipose tissues are not only targets but de novo synthesizing sites of sex steroid(s), though the synthesizing activities could be much less than in gonads. Further researches in this field will be helpful for understanding the adipose physiology and for medical application such as sex-specific steroid supplement therapies for older populations.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.1
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• pp.11-18
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• 2008

We created a cDNA microarray representing approximately 3,500 pig genes for functional genomic studies. The array elements were selected from 6,494 cDNA clones identified in a large-scale expressed sequence tag (EST) project. These cDNA clones came from normalized and subtracted porcine adipose tissue cDNA libraries. Sequence similarity searches of the 3,426 ESTs represented on the array using BLASTN identified 2,790 (81.4%) as putative human orthologs, with the remainder consisting of "novel" genes or highly divergent orthologs. We used the gene microarray to profile transcripts expressed by adipose tissue of fatty Chinese Xiang pig (XP) and muscley Large White (LW). Microarray analysis of RNA extracted from adipose tissue of fatty XP and muscley LW identified 81 genes that were differently expressed two fold or more. Transcriptional differences of four of these genes, adipocyte fatty acid binding protein (aP2), stearyl-CoA desaturase (SCD), sterol regulatory element binding transcription factor 1 (SREBF1) and lipoprotein lipase (LPL) were confirmed using SYBR Green quantitative RT-PCR technology. Our results showed that high expression of SCD and SREBF1 may be one of the reasons that larger fat deposits are observed in the XP. In addition, our findings also illustrate the potential power of microarrays for understanding the molecular mechanisms of porcine development, disease resistance, nutrition, fertility and production traits.

• Journal of Nutrition and Health
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• v.57 no.2
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• pp.171-184
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• 2024

Purpose: Although activating thermogenic adipocytes is a promising strategy to reduce the risk of obesity and related metabolic disorders, emerging evidence suggests that it is difficult to induce adipocyte thermogenesis in obesity. Therefore, this study aimed to investigate the regulation of adipocyte thermogenesis in diet-induced obesity. Methods: Adipose progenitor cells were isolated from the white and brown adipose tissues of control diet (CD) or high-fat diet (HFD) fed mice, and fully differentiated white and brown adipocytes were treated with β-agonists or 18-carbon fatty acids for β-adrenergic activation or peroxisome proliferator-activated receptor (PPAR) activation. Results: Compared to the CD-fed mice, the expression of uncoupling protein 1 (Ucp1) was lower in the white adipose tissue of the HFD-fed mice; however, this was not observed in the brown adipose tissue. The expression of peroxisome proliferator-activated receptor gamma (Pparg) was lower in the brown adipose progenitor cells isolated from HFD-fed mice than in those isolated from the CD-fed mice. Norepinephrine (NE) treatment exerted lesser effect on peroxisome proliferator-activated receptor-γ coactivator (Pgc1a) upregulation in white adipocytes derived from HFD-fed mice than those derived from CD-fed mice. Regardless which 18-carbon fatty acids were treated, the expression levels of thermogenic genes including Ucp1, Pgc1a, and positive regulatory domain zinc finger region protein 16 (Prdm16) were higher in the white adipocytes derived from HFD-fed mice. Oleic acid (OLA) and γ-linolenic acid (GLA) upregulated Pgc1a expression in white adipocytes derived from HFD-fed mice. Brown adipocytes derived from HFD-fed mice had higher expression levels of Pgc1a and Prdm16 compared to their counterparts. Conclusion: These results indicate that diet-induced obesity may downregulate brown adipogenesis and NE-induced thermogenesis in white adipocytes. Also, HFD feeding may induce thermogenic gene expression in white and brown primary adipocytes, and OLA and GLA could augment the expression levels.

• Journal of Microbiology and Biotechnology
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• v.27 no.6
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• pp.1180-1188
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• 2017

Neuronatin (NNAT) is known to regulate ion channels during brain development and plays a role in maintaining the structure of the nervous system. A previous in silico analysis showed that Nnat was overexpressed in the adipose tissue of an obese rodent model relative to the wild type. Therefore, the aim of the present study was to investigate the function of Nnat in the adipose tissue. Because obesity is known to systemically induce low-grade inflammation, the Nnat expression level was examined in the adipose tissue obtained from C57BL/6 mice administered lipopolysaccharide (LPS). Unexpectedly, the Nnat expression level decreased in the white adipose tissue after LPS administration. To determine the role of NNAT in inflammation, 3T3-L1 cells overexpressing Nnat were treated with LPS. The level of the p65 subunit of nuclear factor-kappa B ($NF-{\kappa}B$) and the activity of $NF-{\kappa}B$ luciferase decreased following LPS treatment. These results indicate that NNAT plays an anti-inflammatory role in the adipose tissue.

• Journal of Applied Biological Chemistry
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• v.59 no.1
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• pp.49-56
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• 2016

The current study investigated the anti-obesity effect of Cissus quadrangularsis extracts (CQR-300) and its molecular action mechanism on obese mice induced high-fat diet (HFD). To induce the obesity, mice were fed a HFD for 6 weeks and then fed HFD only or HFD with CQR-300 at 50 and 200 mg/kg. Then, body weight gain and white adipose tissue weights were measured. We investigated the reduction in body fat and the regulation of fatty acid synthesis was measured by dual energy X-ray absorptiometry and real-time PCR with Western blot, respectively. In vitro study, CQR-300 inhibited pancreatic lipase activity. The CQR-300 treatment was significantly decreased the body weight gain and adipocytes size as well as white adipose tissues weights in HFD-induced obese mice. Furthermore, CQR-300 reduced the body fat and fat mass with regulating of adipose tissue hormones as leptin. Treatment with 50 mg/kg CQR-300 showed effectively lower expression levels of adipogenesis/lipogenesis related genes and proteins such as CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$), peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), Sterol regulatory element binding protein-1c (SREBP-1c), and fatty acid synthase (FAS) in white adipose tissue (WAT) as compared with the HFD fed only mice. These results suggest that the CQR-300 has an anti-obesity effect via inhibition of lipase activity, decrease the body fat mass by regulating the adipogenesis and lipogenesis related genes and proteins in epididymal adipose tissue with evaluate body fat reduce in the HFD-induced obese mice.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.9
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• pp.1221-1228
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• 2010

This study aimed to examine the effect of overfeeding on biochemical parameters and lipoprotein-lipase (LPL) mRNA expression in different tissues associated with hepatic lipogenesis in Sichuan white and Landes geese. Fifty healthy male Sichuan white geese and fifty male Landes geese (Cygnus atratus) were hatched on the same day under the same feeding conditions and were selected as experimental animals. After overfeeding for 14 days (from 14 weeks to 16 weeks) and then slaughtering, the biochemical changes of hepatic lipogenesis were evaluated. Results showed that i) in Landes geese, the plasma concentration of glucose was higher (p<0.001), while plasma concentrations of insulin and VLDL were both lower (p<0.01); ii) the LPL mRNA level in pectoralis muscle and leg muscle of the overfed groups in both breeds was higher (p<0.05) than in the control groups; iii) in Sichuan white geese, the proportion of fatty liver weight was positively correlated with plasma triacylglycerols (TG)(p<0.05) and VLDL concentrations (p<0.05), while these correlations were not significant in Landes geese; and iv) the activity of LPL had significant positive correlation with the proportions of lipids in subcutaneous adipose tissue and abdominal adipose tissue in Sichuan white geese, while in Landes geese the correlation was negative (p<0.05) with proportions of lipids in the liver, LPL activity had a significant positive correlation with the proportions of lipids in subcutaneous adipose tissue. These results suggest that the Landes geese have a better ability to use the massive amount of ingested food and to store lipids preferentially in the liver, but the Sichuan white geese have a relatively lower ability to use energetic nutrients and lipid storage is more efficient in the adipose tissues.

• Biomedical Science Letters
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• v.12 no.4
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• pp.319-327
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• 2006

This study aimed to determine whether troglitazone stimulates genes related to fatty acid ${\beta}$-oxidation, leading to modulation of white adipose tissue (WAT) metabolism in high fat diet-fed mice. Female C57BL/6J mice were randomly divided into two groups (n=10/group). After they received either a high fat diet or the same high fat diet supplemented with troglitazone for 4 weeks, the effects of troglitazone on gene expression and physiology of WAT were measured using Northern, histological and serological analyses. Administration of troglitazone induced the expression of genes involved in mitochondrial and peroxisomal fatty acid ${\beta}$-oxidation in mesenteric WAT. Troglitazone also significantly increased uncoupling protein 2 mRNA levels. The changes in WAT gene expression were accompanied by reductions in circulating levels of free fatty acids and triglycerides as well as glucose and insulin. Histological studies showed that troglitazone treatment decreased the average size of adipocytes in mesenteric WAT. These results suggest that troglitazone-stimulated WAT expression of genes associated with fatty acid ${\beta}$-oxidation regulates WAT metabolism of high fat diet-fed mice, contributing to improvement of insulin sensitivity.

• Journal of Convergence Korean Medicine
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• v.5 no.2
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• pp.11-16
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• 2023

Objectives: The purpose of this study was to investigate the anti-obesity effects of the aqueous extract of Schizandra chinensis (SC) in menopausal mice. Methods: To induce menopausal obesity, female mice were ovariectomized (OVX) and fed a high-fat diet (HFD; 60% fat, 28% carbohydrates, 14% protein) for 12 weeks. The mice were divided into 6 groups (n = 8): NOR (sham-operated and vehicle-treated), HFD+OVX (vehicle-treated), E2 (17-beta estradiol 50 ㎍/kg-treated), SC1 (1 mg/kg SC-treated), SC10 (10 mg/kg SC-treated), and SC100 (100 mg/kg SC-treated). Samples were orally administered for 6 weeks, after which all experimental mice were sacrificed. Body weight, feeding efficiency, white adipose tissue weight, adipocyte diameter, and fat vacuoles in liver were analyzed. Results: By treating with SC extract, the body weight and feeding efficiency of mice were significantly decreased. The weight of visceral fat tissues was decreased in the SC10 and SC100 groups. Histopathology showed that fat cell diameters of white adipose tissue were also decreased in the SC10 and SC100 groups. Additionally, SC extract regenerated the hepatocyte damage and decreased the size and number of follicular adipocytes Conclusion: In summary, these results suggest that SC has inhibitory effects against menopausal obesity. Schizandra chinensis may be a potential alternative for obesity among female menopausal diseases.

• BMB Reports
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• v.55 no.10
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• pp.500-505
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• 2022

Uncoupling protein 2 (Ucp2) was first introduced as a member of Uncoupling protein family and a regulator of ROS formation; however, its role in adipose tissue is not fully understood. In the present study, we have investigated the role of Ucp2 against high-fat diet (HFD)-induced obesity in epididymal white adipose tissue (eWAT) and browning of inguinal white adipose tissue (iWAT). Diet-induced obesity is closely related to macrophage infiltration and the secretion of pro-inflammatory cytokines. Macrophages surround adipocytes and form a crown-like-structure (CLS). Some reports have suggested that CLS formation requires adipocyte apoptosis. After 12 weeks of HFD challenge, Ucp2 knockout (KO) mice maintained relatively lean phenotypes compared to wild-type (WT) mice. In eWAT, macrophage infiltration, CLS formation, and inflammatory cytokines were reduced in HFD KO mice compared to HFD WT mice. Surprisingly, we found that apoptotic signals were also reduced in the Ucp2 KO mice. Our study suggests that Ucp2 deficiency may prevent diet-induced obesity by regulating adipocyte apoptosis. However, Ucp2 deficiency did not affect the browning capacity of iWAT.