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Wnt signaling mediates TLR pathway and promote unrestrained adipogenesis and metaflammation: Therapeutic targets for obesity and type 2 diabetes

Aamir K, Khan HU, Sethi G, Hossain MA, Arya A

Pharmacol Res, 2020 02;152:104602.
PMID: 31846761 DOI: 10.1016/j.phrs.2019.104602

Diabesity is the combination of type 2 diabetes and obesity characterized by chronic low-grade inflammation. The Wnt signaling act as an evolutionary pathway playing crucial role in regulating cellular homeostasis and energy balance from hypothalamus to metabolic organs. Aberrant activity of certain appendages in the canonical and non-canonical Wnt system deregulates metabolism and leads to adipose tissue expansion, this key event initiates metabolic stress causing metaflammation and obesity. Metaflammation induced obesity initiates abnormal development of adipocytes mediating through the non-canonical Wnt signaling inhibition of canonical Wnt pathway to fan the flames of adipogenesis. Moreover, activation of toll like receptor (TLR)-4 signaling in metabolic stress invites immune cells to release pro-inflammatory cytokines for recruitment of macrophages in adipose tissues, further causes polarization of macrophages into M1(classically activated) and M2 (alternatively activated) subtypes. These events end with chronic low-grade inflammation which interferes with insulin signaling in metabolic tissues to develop type 2 diabetes. However, there is a dearth in understanding the exact mechanism of Wnt-TLR axis during diabesity. This review dissects the molecular facets of Wnt and TLRs that modulates cellular components during diabesity and provides current progress, challenges and alternative therapeutic strategies at preclinical and clinical level.

Matched MeSH terms: Adipose Tissue
Fulltext Vitamin D status among postmenopausal Malaysian women

Rahman SA, Chee WS, Yassin Z, Chan SP

Asia Pac J Clin Nutr, 2004;13(3):255-60.
PMID: 15331337

Serum levels of 25-hydroxyvitamin D (25 (OH) D) were determined in 276 (103 Malays and 173 Chinese) postmenopausal women, aged 50 to 65 years. The level of 25 (OH) D was significantly lower in the postmenopausal Malay women (44.4 +/-10.6 nmol/L) compared to the Chinese women (68.8 +/- 15.7 nmol/L) (P<0.05). There were 27% Malay women with serum 25 (OH) D in the range of 50 - 100 nmol/L (defined as lowered vitamin D status, or hypovitaminosis D) and 71% with levels in the range of 25 - 50 nmol/L (defined as vitamin D insufficiency) compared to 87% and 11% Chinese women respectively. Serum 25 (OH) D was found to significantly correlate with BMI, fat mass and PTH level. Multivariate analyses showed that race has a strong association with vitamin D status. The high prevalence of inadequate levels of serum vitamin D found in our study may have important public health consequences and warrants the development of a strategy to correct this problem in the older adult Malaysian population.

Matched MeSH terms: Adipose Tissue/metabolism
Fulltext Vitamin D intake and sun exposure among Malaysian athletes in National Sports Institute, Bukit Jalil

Leong, L.W., Loh, S.P., Neng Azhanie, A.

Malaysian Journal of Medicine and Health Sciences, 2013;9(1):21-28.
MyJurnal

Vitamin D plays an important role in maintaining the physical health as well as the performance of athletes. This cross-sectional analytical study was conducted to determine vitamin D intake, sun exposure and skin types of both indoor and outdoor Malaysian athletes in the National Sports Institute, Bukit Jalil. Method: A total of 28 indoor (badminton, shooting, wushu and fencing) and 36 outdoor (athletics, football and hockey) athletes were recruited for this study. The dietary vitamin D intake was estimated using Vitamin D-specific Food Frequency Questionnaire (FFQ). The Sun Exposure Index (SEI) was calculated from Seven-day Sun Exposure Record while the skin types of athletes were determined using Fitzpatrick Skin Typing Questionnaire. Results: The mean age of the athletes was 21.02±4.11 years and their mean Body Mass Index (BMI) was 22.20±2.22 kg/m2. The mean body fat percentage of outdoor athletes was significantly lower than indoor athletes (p

Matched MeSH terms: Adipose Tissue
Fulltext Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats

Atangwho IJ, Yin KB, Umar MI, Ahmad M, Asmawi MZ

BMC Complement Altern Med, 2014;14:426.
PMID: 25358757 DOI: 10.1186/1472-6882-14-426

This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA.

Matched MeSH terms: Adipose Tissue/metabolism
Validity of body composition methods across ethnic population groups

Deurenberg P, Deurenberg-Yap M

Acta Diabetol, 2003 Oct;40 Suppl 1:S246-9.
PMID: 14618484

Most in vivo body composition methods rely on assumptions that may vary among different population groups as well as within the same population group. The assumptions are based on in vitro body composition (carcass) analyses. The majority of body composition studies were performed on Caucasians and much of the information on validity methods and assumptions were available only for this ethnic group. It is assumed that these assumptions are also valid for other ethnic groups. However, if apparent differences across ethnic groups in body composition 'constants' and body composition 'rules' are not taken into account, biased information on body composition will be the result. This in turn may lead to misclassification of obesity or underweight at an individual as well as a population level. There is a need for more cross-ethnic population studies on body composition. Those studies should be carried out carefully, with adequate methodology and standardization for the obtained information to be valuable.

Matched MeSH terms: Adipose Tissue/anatomy & histology
Unique molecular signatures influencing the biological function and fate of post-natal stem cells isolated from different sources

Abu Kasim NH, Govindasamy V, Gnanasegaran N, Musa S, Pradeep PJ, Srijaya TC, et al.

J Tissue Eng Regen Med, 2015 Dec;9(12):E252-66.
PMID: 23229816 DOI: 10.1002/term.1663

The discovery of mesenchymal stem cells (MSCs) from a myriad of tissues has triggered the initiative of establishing tailor-made stem cells for disease-specific therapy. Nevertheless, lack of understanding on the inherent differential propensities of these cells may restrict their clinical outcome. Therefore, a comprehensive study was done to compare the proliferation, differentiation, expression of cell surface markers and gene profiling of stem cells isolated from different sources, viz. bone marrow, Wharton's jelly, adipose tissue and dental pulp. We found that although all MSCs were phenotypically similar to each other, Wharton's jelly (WJ) MSCs and dental pulp stem cells (DPSCs) were highly proliferative as compared to bone marrow (BM) MSCs and adipose tissue (AD) MSCs. Moreover, indistinguishable cell surface characteristics and differentiation capacity were confirmed to be similar among all cell types. Based on gene expression profiling, we postulate that BM-MSCs constitutively expressed genes related to inflammation and immunodulation, whereas genes implicated in tissue development were highly expressed in AD-MSCs. Furthermore, the transcriptome profiling of WJ-MSCs and DPSCs revealed an inherent bias towards the neuro-ectoderm lineage. Based on our findings, we believe that there is no unique master mesenchymal stem cell that is appropriate to treat all target diseases. More precisely, MSCs from different sources exhibit distinct and unique gene expression signatures that make them competent to give rise to specific lineages rather than others. Therefore, stem cells should be subjected to rigorous characterization and utmost vigilance needs to be adopted in order to choose the best cellular source for a particular disease.

Matched MeSH terms: Adipose Tissue/cytology; Adipose Tissue/metabolism*
Fulltext Ultra-processed food consumption in relation to BMI and body fat percentage of adults in Terengganu

Asma’ Ali, Nurul Atiqah Khasbullah, Fauziah Tufail Ahmad, Hayati Mohd Yusof

Malaysian Journal of Medicine and Health Sciences, 2020;16(1):37-43.
MyJurnal

Introduction: There is an emergent increase of ultra-processed food consumption in developing countries including Malaysia which carries a likelihood towards the increase of obesity. However, few studies have been done in relating between ultra-processed consumption and obesity, especially in Malaysia. Therefore, this study aims to determine the consumption of ultra-processed foods and its relationship with BMI and body fat percentage among university committee in Kuala Nerus, Terengganu. Methods: A cross-sectional study was performed among 167 individuals aged 18 to 59 years old in Kuala Nerus. Data were collected using a researcher-administered questionnaire which consisted of three different sections: socio-demographic profile, two days 24-hour dietary recall, and nutritional status assessment on BMI and body fat percentage. Consumption of ultra-processed foods were determined by classifying two days 24-hour dietary recall based on ultra-processed food classification. Data were analyzed using SPSS version 21.0 with p

Matched MeSH terms: Adipose Tissue
Fulltext Treatment of spinal cord injury with mesenchymal stem cells

Liau LL, Looi QH, Chia WC, Subramaniam T, Ng MH, Law JX

Cell Biosci, 2020;10:112.
PMID: 32983406 DOI: 10.1186/s13578-020-00475-3

Background: Spinal cord injury (SCI) is the damage to the spinal cord that can lead to temporary or permanent loss of function due to injury to the nerve. The SCI patients are often associated with poor quality of life.
Results: This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue.
Conclusion: These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.

Matched MeSH terms: Adipose Tissue
Transcriptomics expression analysis to unveil the molecular mechanisms underlying the cocoa polyphenol treatment in diet-induced obesity rats

Ali F, Ismail A, Esa NM, Pei CP

Genomics, 2015 Jan;105(1):23-30.
PMID: 25451742 DOI: 10.1016/j.ygeno.2014.11.002

Cocoa polyphenol (CP), due to their biological actions, may be supplementary treatments for adipose tissue-fat gain. However, the molecular mechanism of CPs is still ambiguous. This study investigated the hypothesis that CP treatment modulates expressing of lipid metabolism genes in mesenteric white adipose tissue (MES-WAT). Sprague-Dawley (SD) rats were fed a low-fat (LF) or high-fat (HF) diet for 12 weeks. Thereafter, HFD rats (n = 10/group) were treated at a dose of 600 mg/kg bw/day CPs (HFD + CPs) for 4 weeks. DNA microarray analysis resulted in 753 genes of the 13,008 genes expressed. Bioinformatics tools showed CP treatment significantly decreased gene expression levels for lipogenic enzymes, while increased the mRNA levels responsible for lipolysis enzymes. CP administration differentially regulates gene expression involved in lipid metabolism in MES-WAT. These data unveil a new insight into the molecular mechanisms underlying the pharmacological effect of CPs on obesity biomarkers in obese rats.

Matched MeSH terms: Adipose Tissue, White/metabolism
Fulltext Transcriptomics analysis of differentially expressed genes in subcutaneous and perirenal adipose tissue of sheep as affected by their pre- and early postnatal malnutrition histories

Ahmad S, Drag MH, Salleh SM, Cai Z, Nielsen MO

BMC Genomics, 2021 May 11;22(1):338.
PMID: 33975549 DOI: 10.1186/s12864-021-07672-5

BACKGROUND: Early life malnutrition is known to target adipose tissue with varying impact depending on timing of the insult. This study aimed to identify differentially expressed genes in subcutaneous (SUB) and perirenal (PER) adipose tissue of 2.5-years old sheep to elucidate the biology underlying differential impacts of late gestation versus early postnatal malnutrition on functional development of adipose tissues. Adipose tissues were obtained from 37 adult sheep born as twins to dams fed either NORM (fulfilling energy and protein requirements), LOW (50% of NORM) or HIGH (110% of protein and 150% of energy requirements) diets in the last 6-weeks of gestation. From day 3 to 6 months of age, lambs were fed high-carbohydrate-high-fat (HCHF) or moderate low-fat (CONV) diets, and thereafter the same moderate low-fat diet.
RESULTS: The gene expression profile of SUB in the adult sheep was not affected by the pre- or early postnatal nutrition history. In PER, 993 and 186 differentially expressed genes (DEGs) were identified in LOW versus HIGH and NORM, respectively, but no DEG was found between HIGH and NORM. DEGs identified in the mismatched pre- and postnatal nutrition groups LOW-HCHF (101) and HIGH-HCHF (192) were largely downregulated compared to NORM-CONV. Out of 831 DEGs, 595 and 236 were up- and downregulated in HCHF versus CONV, respectively. The functional enrichment analyses revealed that transmembrane (ion) transport activities, motor activities related to cytoskeletal and spermatozoa function (microtubules and the cytoskeletal motor protein, dynein), and responsiveness to the (micro) environmental extracellular conditions, including endocrine and nervous stimuli were enriched in the DEGs of LOW versus HIGH and NORM. We confirmed that mismatched pre- and postnatal feeding was associated with long-term programming of adipose tissue remodeling and immunity-related pathways. In agreement with phenotypic measurements, early postnatal HCHF feeding targeted pathways involved in kidney cell differentiation, and mismatched LOW-HCHF sheep had specific impairments in cholesterol metabolism pathways.
CONCLUSIONS: Both pre- and postnatal malnutrition differentially programmed (patho-) physiological pathways with implications for adipose functional development associated with metabolic dysfunctions, and PER was a major target.

Matched MeSH terms: Adipose Tissue
Fulltext Tocotrienol levels in adipose tissue of benign and malignant breast lumps in patients in Malaysia

Nesaretnam K, Gomez PA, Selvaduray KR, Razak GA

Asia Pac J Clin Nutr, 2007;16(3):498-504.
PMID: 17704032

Data on dietary exposure to vitamin E by plasma or adipose tissue concentrations of alpha-tocopherol (alpha-T) in observational studies have failed to provide consistent support for the idea that alpha-T provides women with any protection from breast cancer. In contrast, studies indicate that alpha, gamma, and delta-tocotrienols but not alpha-T have potent anti-proliferative effects in human breast cancer cells. Our aim was to investigate whether there was a difference in tocopherol and tocotrienol concentrations in malignant and benign adipose tissue, in a Malaysian population consuming predominantly a palm oil diet. The study was undertaken using fatty acid levels in breast adipose tissue as a biomarker of qualitative dietary intake of fatty acids. The major fatty acids in breast adipose tissue of patients (benign and malignant) were oleic acid (45-46%), palmitic (28-29%) and linoleic (11-12%). No differences were evident in the fatty acid composition of the two groups. There was a significant difference (p=0.006) in the total tocotrienol levels between malignant (13.7 +/- 6.0 microg/g) and benign (20+/-6.0 microg/g) adipose tissue samples. However, no significant differences were seen in the total tocopherol levels (p=0.42) in the two groups. The study reveals that dietary intake influences adipose tissue fatty acid levels and that adipose tissue is a dynamic reservoir of fat soluble nutrients. The higher adipose tissue concentrations of tocotrienols in benign patients provide support for the idea that tocotrienols may provide protection against breast cancer.

Matched MeSH terms: Adipose Tissue/chemistry*
Fulltext Therapeutic Potential of Bama Pig Adipose-Derived Mesenchymal Stem Cells for the Treatment of Carbon Tetrachloride-Induced Liver Fibrosis

Wu X, Zhang S, Lai J, Lu H, Sun Y, Guan W

Exp Clin Transplant, 2020 12;18(7):823-831.
PMID: 33349209 DOI: 10.6002/ect.2020.0108

OBJECTIVES: Liver fibrosis is inevitable in the healing process of liver injury. Liver fibrosis will develop into liver cirrhosis unless the damaging factors are removed. This study investigated the potential therapy of Bama pig adipose-derived mesenchymal stem cells in a carbon tetrachloride-induced liver fibrosis Institute of Cancer Research strain mice model.
MATERIALS AND METHODS: Adipose-derived mesenchymal stem cells were injected intravenously into the tails of mice of the Institute of Cancer Research strain that had been treated with carbon tetrachloride for 4 weeks. Survival rate, migration, and proliferation of adipose-derived mesenchymal stem cells in the liver were observed by histochemistry, fluorescent labeling, and serological detection.
RESULTS: At 1, 2, and 3 weeks after adipose-derived mesenchymal stem cell injection, liver fibrosis was significantly ameliorated. The injected adipose-derived mesenchymal stem cells had hepatic differentiation potential in vivo, and the survival rate of adipose-derived mesenchymal stem cells declined over time.
CONCLUSIONS: The findings in this study confirmed that adipose-derived mesenchymal stem cells derived from the Bama pig can be used in the treatment of liver fibrosis, and the grafted adipose-derived mesenchy-mal stem cells can migrate, survive, and differentiate into hepatic cells in vivo.

Matched MeSH terms: Adipose Tissue/cytology*
The supplementation of levothyroxine among indigenous people in endemic goitre areas: The impact of therapy

Zaleha MI, Osman A, Iskandar ZA, Sazali S, Ali MM, Roslan I, et al.

Asia Pac J Clin Nutr, 1998 Jun;7(2):138-50.
PMID: 24393641

In order to study the effect of levothyroxine in the treatment of endemic goitre, a longitudinal study was conducted among the Aborigines in Lanai Post and Sinderut Post, situated in an iodine-deficient area located in the district of Kuala Lipis, Pahang. All subjects in the treatment group (Lanai Post) were given 100 µg of levothyroxine per day and were followed for 1 1/2 years. A total of 311 subjects were examined at baseline, 323 on the first, 256 on the second, 239 on the third and 184 on the fourth visit following levothyroxine supplementation. Goitre prevalence, thyroid hormones, thyroid volume, nutritional status, urinary iodine levels, arterial blood pressure and mental performance were determined. Following the intervention, goitre prevalence was significantly reduced in the treatment group (baseline 42.8% vs final visit 13.0%, p<0.0001); however, no significant difference was noted in the control group. Total T4 levels were increased in the treatment group (p<0.0001), while a significant reduction was noted in the control group (p<0.0001). Thyroid-stimulating hormone levels increased significantly in the treatment group following 1 year of intervention, while no significant changes were observed in the control group. As for the thyroid volume, both groups showed a significant increment following the intervention (p<0.0001). With respect to the nutritional status, the treatment group showed a significant increase in body weight following the intervention (p<0.05). In addition, the mid-arm circumference and body mass index also increased after 1 year of intervention. However, the control group showed a reduction in the waist-hip ratio (p<0.0001). Although there was no statistical difference in the waist-hip ratio in the treatment group, there has been a significant reduction observed after 1 year of intervention. At 1 year, a reduction in skinfold thickness was noted in the treatment group while only the triceps and subscapular were increased in the control group. The body fat was decreased in the treatment group following 1 year of intervention (p<0.0001). No particular trend was noted in the urinary iodine excretion in the treatment group, but surprisingly, the levels were increased in the control group (p<0.0001). A significant increase in both systolic and diastolic blood pressures was observed in the treatment group following 1 year of intervention, but the controls showed a reduction in the systolic blood pressure (p<0.0001). Both groups showed a remarkable increase in mental performance, with a more pronounced effect in the treatment group (p<0.05). The correction of iodine deficiency by levothyroxine supplementation has a short-term beneficial effect in reducing the prevalence of goitre and improving the mental ability among the Aborigines in endemic areas; however, proper monitoring and close supervision are needed to maintain compliance.

Matched MeSH terms: Adipose Tissue
The relationship between circulating testosterone and inflammatory cytokines in men

Mohamad NV, Wong SK, Wan Hasan WN, Jolly JJ, Nur-Farhana MF, Ima-Nirwana S, et al.

Aging Male, 2019 Jun;22(2):129-140.
PMID: 29925283 DOI: 10.1080/13685538.2018.1482487

Testosterone is the predominant gonadal androgen in men. Low testosterone levels are found to be associated with an increased in metabolic risk and systematic inflammation. Since adipose tissue is a source of inflammatory cytokines, testosterone may regulate inflammation by acting on adipose tissue. This review aimed to explore the role of testosterone in inflammation and its mechanism of action. Both animal studies and human studies showed that (1) testosterone deficiency was associated with an increase in pro-inflammatory cytokines; (2) testosterone substitution reduced pro-inflammatory cytokines. The suppression of inflammation by testosterone were observed in patients with coronary artery disease, prostate cancer and diabetes mellitus through the increase in anti-inflammatory cytokines (IL-10) and the decrease in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Despite these, some studies also reported a non-significant relationship. In conclusion, testosterone may possess anti-inflammatory properties but its magnitude is debatable. More evidence is needed to validate the use of testosterone as a marker and in the management of chronic inflammatory diseases.

Matched MeSH terms: Adipose Tissue/metabolism
Fulltext The physiology of leptin: revisited

Singh, Harbindar Jeet

Medical Health Reviews, 2009;2009(1):95-133.
MyJurnal

Leptin, a 167 amino-acid product of the ob or LEP gene, was first reported in 1994 after a 40-year search that began following the emergence of a mutant strain of mice with hyperphagia, early on-set obesity, and delayed sexual maturation. Since then, leptin deficiency has also been reported in the rat, and more recently in humans. It is secreted constitutively primarily by the white adipose tissue, and in smaller quantities by a number of non-adipose tissues. It acts by binding to specific membrane bound leptin receptors, belonging to the class 1 cytokine receptor family, and activating the JAK-STAT system. Leptin regulates appetite and body weight mainly through its actions on the hypothalamus involving the NPYmelanocortin pathway, and, to a lesser extent, through increased energy expenditure by way of sympathoactivation and increased substrate cycling. Its effects on reproduction, puberty in particular, are mediated through actions on the hypothalamic-pituitary-gonadal axis and on the gonads. Leptin also appears to have permissive roles in CNS development during the neonatal period, bone growth and development, and in haemopoietic and immune functions. Although it was its deficiency state that first led to its discovery, it now appears that the clinical significance of leptin lies not only in the consequences of its deficiency but also when it is in excess as occurs in obesity. Emerging evidence is implicating leptin as a link between obesity associated cardiovascular disease risks and infertility. Besides this, leptin is also being implicated as a growth factor in cancer. The story that started with a search for a body weight regulating factor is now unfolding into one that is revealing roles for leptin that stretch beyond the regulation of appetite and body weight.

Matched MeSH terms: Adipose Tissue, White
The paradox of low body mass index and high body fat percentage among Chinese, Malays and Indians in Singapore

Deurenberg-Yap M, Schmidt G, van Staveren WA, Deurenberg P

Int. J. Obes. Relat. Metab. Disord., 2000 Aug;24(8):1011-7.
PMID: 10951540

OBJECTIVE: To study the relationship between body fat percentage and body mass index (BMI) in three different ethnic groups in Singapore (Chinese, Malays and Indians) in order to evaluate the validity of the BMI cut-off points for obesity.
DESIGN: Cross-sectional study.
SUBJECTS: Two-hundred and ninety-one subjects, purposively selected to ensure adequate representation of range of age and BMI of the general adult population, with almost equal numbers from each ethnic and gender group.
MEASUREMENTS: Body weight, body height, sitting height, wrist and femoral widths, skinfold thicknesses, total body water by deuterium oxide dilution, densitometry with Bodpod(R) and bone mineral content with Hologic(R) QDR-4500. Body fat percentage was calculated using a four-compartment model.
RESULTS: Compared with body fat percentage (BF%) obtained using the reference method, BF% for the Singaporean Chinese, Malays and Indians were under-predicted by BMI, sex and age when an equation developed in a Caucasian population was used. The mean prediction error ranged from 2.7% to 5.6% body fat. The BMI/BF% relationship was also different among the three Singaporean groups, with Indians having the highest BF% and Chinese the lowest for the same BMI. These differences could be ascribed to differences in body build. It was also found that for the same amount of body fat as Caucasians who have a body mass index (BMI) of 30 kg/m2 (cut-off for obesity as defined by WHO), the BMI cut-off points for obesity would have to be about 27 kg/m2 for Chinese and Malays and 26 kg/m2 for Indians.
CONCLUSIONS: The results show that the relationship between BF% and BMI is different between Singaporeans and Caucasians and also among the three ethnic groups in Singapore. If obesity is regarded as an excess of body fat and not as an excess of weight (increased BMI), the cut-off points for obesity in Singapore based on the BMI would need to be lowered. This would have immense public health implications in terms of policy related to obesity prevention and management.

Matched MeSH terms: Adipose Tissue*
The mRNA expression of soluble urokinase plasminogen activator surface receptor in human adipose tissue is positively correlated with body mass index

Ng HF, Chin KF, Chan KG, Ngeow YF

Genome, 2015 Jun;58(6):315-21.
PMID: 26284904 DOI: 10.1139/gen-2015-0028

suPLAUR is the transcript variant that encodes the soluble form of the urokinase plasminogen activator surface receptor (suPLAUR). This soluble protein has been shown to enhance leukocyte migration and adhesion, and its circulatory level is increased in inflammatory states. In this pilot study, we used RNA-Seq to examine the splicing pattern of PLAUR in omental adipose tissues from obese and lean individuals. Of the three transcript variants of the PLAUR gene, only the proportion of suPLAUR (transcript variant 2) increases in obesity. After removing the effects of gender and age, the expression of suPLAUR is positively correlated with body mass index. This observation was validated using RT-qPCR with an independent cohort of samples. Additionally, in our RNA-Seq differential expression analysis, we also observed, in obese adipose tissues, an up-regulation of genes encoding other proteins involved in the process of chemotaxis and leukocyte adhesion; of particular interest is the integrin beta 2 (ITGB2) that is known to interact with suPLAUR in leukocyte adhesion. These findings suggest an important role for suPLAUR in the recruitment of immune cells to obese adipose tissue, in the pathogenesis of obesity.

Matched MeSH terms: Adipose Tissue/metabolism*
The interaction between energy intake, physical activity and UCP2 -866G/A gene variation on weight gain and changes in adiposity: an Indonesian Nutrigenetic Cohort (INDOGENIC)

Muhammad HFL, Sulistyoningrum DC, Huriyati E, Lee YY, Muda WAMW

Br J Nutr, 2021 03 28;125(6):611-617.
PMID: 32746947 DOI: 10.1017/S0007114520003104

The present study aimed to investigate an interaction between energy intake, physical activity and UCP2 gene variation on weight gain and adiposity changes in Indonesian adults. This is a prospective cohort study conducted in 323 healthy adults living in the city of Yogyakarta, Indonesia. Energy intake, physical activity, body weight, BMI, percentage body fat and waist:hip ratio (WHR) were measured at baseline and after 2 years while UCP2 -866G/A gene variation was determined at baseline. We reported that after 2 years subjects had a significant increment in body weight, BMI, body fat and reduction in WHR (all P < 0·05). In all subjects, total energy intake was significantly correlated with changes in body weight (β = 0·128, P = 0·023) and body fat (β = 0·123, P = 0·030). Among subjects with the GG genotype, changes in energy intake were positively correlated with changes in body weight (β = 0·232, P = 0·016) and body fat (β = 0·201, P = 0·034). These correlations were insignificant among those with AA + GA genotypes (all P > 0·05). In summary, we show that UCP2 gene variation might influence the adiposity response towards changes in energy intake. Subjects with the GG genotype of UCP2 -866G/A gene were more responsive to energy intake, thus more prone to weight gain due to overeating.

Matched MeSH terms: Adipose Tissue
The impact of long-term in vitro expansion on the senescence-associated markers of human adipose-derived stem cells

Safwani WK, Makpol S, Sathapan S, Chua KH

Appl Biochem Biotechnol, 2012 Apr;166(8):2101-13.
PMID: 22391697 DOI: 10.1007/s12010-012-9637-4

Human adipose-derived stem cells (ASCs) have generated a great deal of excitement in regenerative medicine. However, their safety and efficacy issue remain a major concern especially after long-term in vitro expansion. The aim of this study was to investigate the fundamental changes of ASCs in long-term culture by studying the morphological feature, growth kinetic, surface marker expressions, expression level of the senescence-associated genes, cell cycle distribution and ß-galactosidase activity. Human ASCs were harvested from lipoaspirate obtained from 6 patients. All the parameters mentioned above were measured at P5, P10, P15 and P20. Data were subjected to one-way analysis of variance with a Tukey post hoc test to determine significance difference (P < 0.05). The data showed that growth of ASCs reduced in long-term culture and the ß-galactosidase activity was significantly increased at later passage (P20). The morphology of ASCs in long-term culture showed the manifestation of senescent feature at P15 and P20. Significant alteration in the senescence-associated genes expression levels was observed in MMP1, p21, Rb and Cyclin D1 at P15 and P20. Significant increase in CD45 and HLA DR DQ DP surface marker was observed at P20. While cell cycle analysis showed significant decrease in percentage of ASCs at S and G2/M phase at later passage (P15). Our data showed ASCs cultured beyond P10 favours the senescence pathway and its clinical usage in cell-based therapy may be limited.

Matched MeSH terms: Adipose Tissue/cytology*
The fate of adipose tissue and adipose-derived stem cells in allograft

Farhana S, Kai YC, Kadir R, Sulaiman WAW, Nordin NA, Nasir NAM

Cell Tissue Res, 2023 Nov;394(2):269-292.
PMID: 37624425 DOI: 10.1007/s00441-023-03827-w

Utilizing adipose tissue and adipose-derived stem cells (ADSCs) turned into a promising field of allograft in recent years. The therapeutic potential of adipose tissue and ADSCs is governed by their molecular secretions, ability to sustain multi-differentiation and self-renewal which are pivotal in reconstructive, genetic diseases, and cosmetic goals. However, revisiting the existing functional capacity of adipose tissue and ADSCs and their intricate relationship with allograft is crucial to figure out the remarkable question of safety to use in allograft due to the growing evidence of interactions between tumor microenvironment and ADSCs. For instance, the molecular secretions of adipose tissue and ADSCs induce angiogenesis, create growth factors, and control the inflammatory response; it has now been well determined. Though the existing preclinical allograft studies gave positive feedback, ADSCs and adipose tissue are attracted by some factors of tumor stroma. Moreover, allorecognition is pivotal to allograft rejection which is carried out by costimulation in a complement-dependent way and leads to the destruction of the donor cells. However, extensive preclinical trials of adipose tissue and ADSCs in allograft at molecular level are still limited. Hence, comprehensive immunomodulatory analysis could ensure the successful allograft of adipose tissue and ADSCs avoiding the oncological risk.

Matched MeSH terms: Adipose Tissue*

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