Matrix Metalloproteinase-9 Testing of Golden Rice Cookies With Piper Crocatum Active Extract for Preventing Foot Ulcers in Patients With Diabetes: Protocol for a Randomized Controlled Trial.

BACKGROUND: Diabetic foot ulcers (DFUs) present a formidable challenge to both patients and health care systems. DFUs significantly reduce the quality of life for patients, prolong hospital stays, and are the cause of approximately 70,000 lower limb amputations across the globe annually. Prevention of DFUs primarily involves the optimization of blood sugar levels and the effective management of complications, particularly peripheral neuropathy. Golden Rice has been proven to lower blood sugar levels due to its beta-carotene content, and Piper crocatum (P. crocatum) has been found to be effective in reducing the risk factors of DFUs through biomolecular regulation because of its polyphenol content. OBJECTIVE: The principal objective of this study is to identify the efficacy of P. crocatum-enriched cookies, with Golden Rice as their primary ingredient, in preventing DFUs. The evaluation will center on their impact on the expression of matrix metalloproteinase-9 (MMP-9), a pivotal factor in the development of DFUs. METHODS: This study is an experimental clinical research that follows the randomized controlled trial method and uses a single-blind design. The participants in the study are outpatients from primary health centers in Makassar, Indonesia, who have been diagnosed with diabetes mellitus. The sample for the study will be randomly selected and subsequently categorized into 2 groups: the intervention group and the control group. The intervention group consumes P. crocatum-enriched Golden Rice cookies, while the control group receives cookies without these additives. The participants from both groups will consume their respective cookies (packaged identically) twice a day for 14 days. The cookies will be prepared according to a modified recipe with an emphasis on low glucose content, resulting in 51 calories per cookie, comprising 1% carbohydrates, 6% fat, 4% cholesterol, and 4% fiber, excluding gluten, sugar, and salt. They will be baked at 158°C for 20 minutes. The process involves the addition of 20% Golden Rice and 10% P. crocatum ethanol extract, both prepared via maceration with 96% ethanol. The dependent variable in this study is the expression of gelatinases matrix metalloproteinase, to be assessed at 2 distinct time points-preintervention (pretest) and postintervention (posttest)-with the evaluation conducted through the western blotting method. RESULTS: The recruitment and testing phase started in January 2024. The study is scheduled to be completed by the end of March 2024. Data analysis will commence in April 2024, and the publication of the results is anticipated in the same year (2024). The study will report on the changes in primary data, encompassing gelatinases matrix metalloproteinase, as well as secondary data, including the ankle-brachial index, neuropathy score, and random blood glucose level. CONCLUSIONS: The findings of this trial are expected to significantly impact the selection of strategies by health care practitioners to enhance diabetes self-management, particularly in the domain of therapeutic snacking, for patients diagnosed with diabetes mellitus. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20230502001; https://www.thaiclinicaltrials.org/show/TCTR20230502001. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/49940.

Hypnotherapy influence on maternal psychological, breastfeeding, mRNA-OXTR expression, and OXTR protein.

Hypnotherapy has emerged as a potential alternative to improve exclusive breastfeeding rates, particularly in countries like Indonesia where they are below optimal levels. This study aims to evaluate the impact of audio hypnotherapy on the psychological, exclusive breastfeeding behavior, the OXTR protein and mRNA expression gene OXTR in mothers of infants aged 0-6 months. This study employed a Pragmatic Randomized Controlled Trial design, conducted from November 2022 to May 2023 in 11 primary health centers. The study population included breastfeeding mothers with infants aged 0-6 months, with a total sample size of 70 respondents who were randomly divided into intervention (received audio hypnotherapy) and control groups (received standard care). The psychological condition was measured using the Depression Anxiety Stress Scale. Exclusive breastfeeding behavior was assessed based on both quality and quantity. Genetic factors were evaluated through mRNA OXTR expression using real-time PCR and protein OXTR levels using ELISA. Analyzing data using linear and logistic regression models. Both bivariate and multivariate analyses revealed significant differences in psychological condition (p < .0001). There were big differences in the exclusive breastfeeding behavior (p < .0001), as well as in the amounts of protein OXTR and mRNA expression of the OXTR gene (p < .0001). We recommend the implementation of audio hypnotherapy as an effective complementary therapeutic approach to manage the psychological well-being, exclusive breastfeeding behavior, the mRNA expression of the OXTR gene and levels of OXTR protein in mothers of infants aged 0-6 months.

Decreasing mRNA HMGB1 expression in Klebsiella pneumoniae infection treated by Miana (Coleus scutellarioides (L.) Benth): a cohort experimental study.

Pneumonia is one of the most common infections caused by the bacterium Klebsiella pneumoniae. During the initiation of an infection, the immune system recognizes the pathogen through the release of high mobility group box 1 (HMGB1), thereby triggering the inflammation process. Miana has demonstrated potent inhibitory effects on the inflammatory process during infection in animal models. The aim of this study was to determine the effect of Miana leaf extract on mRNA HMGB1 expression in Balb/c mice infected with K. pneumoniae. Methods: This study comprised a cohort experiment using 20 Balb/c mice divided into four groups. Balb/c mice in each group were intraperitoneally injected with K. pneumoniae. Group 1 was given a placebo; Group 2 was given Miana; Group 3 was given levofloxacin; and Group 4 was given both levofloxacin and Miana. The levels of mRNA HMGB1 expression were measured using real-time PCR before, during, and after the infection as well as after the treatments. Results: The initial examination results showed that the average level of mRNA HMGB1 expression was 5.51 fc. The mRNA HMGB1 expression in mice after being challenged with K. pneumoniae was 9.64 fc. Group 1 that was given a placebo had a mean mRNA HMGB1 expression level of 14.99 fc. Group 2 that was given Miana had a mean mRNA HMGB1 expression level of 13.95 fc. Group 3 that was given levofloxacin had an average mRNA HMGB1 expression level of 6.45 fc, and Group 4 that was given levofloxacin and Miana together had an average mRNA HMGB1 expression level of 5.59 fc. Conclusion: Miana (Coleus scutellarioides (L.) Benth) increased mRNA HMGB1 expression at the initial administration via regulation of the immune system. Administration of Miana following K. pneumoniae infection inhibited the increase in mRNA HMGB1 expression. Treatment with levofloxacin reduced the level of mRNA HMGB1 expression, and the effect was optimized by the administration of Miana leaf extract as a supplement.

Dietary Patterns and Ultra-Processed Foods Consumption in Modern and Traditional Populations in South Sulawesi: An Analysis of Nutritional Status and Body Composition / Patrones dietéticos y consumo de alimentos ultraprocesados en poblaciones modernas y tradicionales de Sulawesi del Sur: un análisis del estado nutricional y la composición corporal

Backgrounds and aim: Dietary patterns play an important role in the emergence of non-communicable diseases such as obesity, hypertension, and metabolic syndrome. This study aims to examine the impact of ultra-processed food on the nutritional status and body composition of modern and traditional population groups in Indonesia. Methods: The study has received ethical approval from the Research Ethics Commission of the Faculty of Medicine, Hasanuddin University with ethics number No.633/UN4.6.4.5.31/PP36/2022. The inclusion criteria in this study included: people in the Makassar population > 50 years old. Exclusion criteria were (1) having chronic gastrointestinal disease/chronic inflammation, (2) having Diabetes Mellitus, (3) consuming antibiotics in the last 3 months, (4) consuming prebiotics/probiotics, (5) having income > IDR 3,400.000,-, (6) rarely (<1x/week) consumes UPF.About 100 samples were taken from people over 50 years old, where 50 samples were taken from both the modern group and the traditional group. To evaluate the dietary pattern, the diet of the sampling persons was analyzed by using a semi-quantitative Food Frequency Questionnaire (SQ-FFQ), and a 24-hours food recall (FR) to examine the food intake. Body Mass Index (BMI) and Waist Circumference (WC) were used to determine the nutritional status, while the body composition was assessed by Tanita BC 730. Results: According to the scatter plot, the higher the ultra-processed food energy consumed, the higher the BMI, Waist Circumference, and Fat Mass results, with the respective effects of 18.4%, 35.3%, and 13.7%. From this study, it was found that there were significant differences (p<0.05) between the traditional and modern groups in all variables except for height based on the independent t-test found no significant difference (p>0.05). Conclusions: In conclusion, dietary patterns with higher consumption of ultra-processed foods influence the increase of body mass index, waist circumference...(AU)

Effect of Probiotic Adjuvant Therapy on Improvement of Clinical Symptoms & Interleukin 6 Levels in Patients With Schizophrenia.

OBJECTIVE: This study aims to examine the effect of giving probiotic adjuvant therapy on improving clinical symptoms & IL-6 levels in patients with schizophrenia. METHODS: This research was a double-blind, placebo-controlled trial conducted at Dadi Psychiatric Hospital, South Sulawesi Province, Indonesia in November-December 2021. The sample of the research was patients with schizophrenia undergoing hospitalization who received therapeutic doses of risperidone with a total of 21 samples in each treatment and control group. Research subjects were measured with Positive and Negative Syndrome Scale (PANSS) at baseline, 2nd, 4th, and 6th weeks. The treatment group received one capsule/12 hours/oral of probiotics for six weeks and the control group received 1 capsule/12 hours/oral placebo for 6 weeks. In addition, two measurements of IL-6 using enzyme-linked immunosorbent assay were performed in both groups, namely at the beginning of week 0 and the end of the 6th week. RESULTS: We found the decrease in the PANSS value which described the improvement in clinical symptoms of the schizophrenic group after receiving therapeutic doses of antipsychotics and probiotic capsules or the treatment group as well as the schizophrenia group receiving therapeutic doses of antipsychotics and placebo capsules or the control group. CONCLUSION: Improvements in clinical symptoms and decreased levels of IL-6 in the group of patients with schizophrenia who received risperidone with probiotic adjuvant therapy were better than in the group of patients with schizophrenia who received risperidone without probiotics as adjuvant therapy.

Overview of Anemia; risk factors and solution offering.

OBJECTIVE: The study aims to determine the picture risk factor-related anemia and the solution offered by searching the literature and reviewing it. METHOD: using literature studies. Article searches using online data-based Science Direct, PubMed, and Google Scholar from 2019 to 2021. They have obtained as many as 20 articles based on inclusion criteria and relevance. RESULT: Anaemia in young women is still a severe problem among the community. There need to be early detection measures to quickly determine the incidence of anemia and describe anemia as one of the information for all circles young women. Women have a higher risk of anemia, especially young women. This is due to strict dietary habits to prevent weight gain, resulting in malnutrition due to the unmet intake of essential nutrients for the body. Whereas in adolescence, there is an increase in iron demand due to growth and menstruation. Therefore it is very important to provide smart solutions to the incidence of anemia. One that is offered is early detection so that prevention can be done. The use of information technology can be used to conduct early detection of anemia in adolescents because it has been widely utilized among the community, especially adolescents. CONCLUSION: From the entire literature review, it seems that nutritional status greatly influences the incidence of anemia suffered, and young women are a target for the best intervention. Early detection and use of technology are innovative solutions offered.

Malnutrition in children associated with low insulin-like growth factor binding protein-3 (IGFBP-3) levels.

OBJECTIVE: This study aimed to compare serum levels of Insulin-like Growth Factor Binding Protein-3 in children with malnutrition and good nutritional status. METHOD: This cross-sectional study included 41 participants consisting of 31 malnourished, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. IGFBP-3 levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULT: Median serum IGFBP-3 levels in malnourished children were found to be lower i.e. 0.35mcg/mL (minimum-maximum: 0.04-1.52mcg/mL) compared to well-nourished children 1.52ng/mL (minimum-maximum 0.47-3.17mcg/mL). CONCLUSION: Serum IGFBP-3 levels can be used as indicators to assess nutritional status.

Leptin levels in children with malnutrition.

OBJECTIVE: This study aimed at comparing serum levels of leptin in children with malnutrition and good nutritional status. METHOD: This cross-sectional study included 41 participants consisting of 31 malnutrition, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. Leptin levels were determined by ELISA (Enzyme-Linked Immunosorbent Assay) method. RESULTS: Median serum leptin level for malnutrition children were found to be lower, i.e., 9.23 (6.02-197.2) ng/mL compared to well-nourished children 30.95 (6.02-89.36) ng/mL. CONCLUSION: Serum leptin levels can be used as indicators to assess nutritional status.

Malnutrition in children associated with low growth hormone (Gh) Levels.

OBJECTIVE: This study aimed to compare serum levels of Growth Hormone in children with malnutrition and good nutritional status. METHOD: This cross-sectional study included 41 participants consisting of 31 malnourished, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. GH levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULT: Median serum GH levels in malnourished children were found to be lower i.e. 1.25ng/mL (minimum-maximum: 0.10-6.19ng/mL) compared to well-nourished children 11.01ng/mL (1.72-15.64ng/mL). CONCLUSION: Serum GH levels can be used as indicators to assess nutritional status.

Astaxanthin, a Marine Carotenoid, Maintains the Tolerance and Integrity of Adipose Tissue and Contributes to Its Healthy Functions.

Recently, obesity-induced insulin resistance, type 2 diabetes, and cardiovascular disease have become major social problems. We have previously shown that Astaxanthin (AX), which is a natural antioxidant, significantly ameliorates obesity-induced glucose intolerance and insulin resistance. It is well known that AX is a strong lipophilic antioxidant and has been shown to be beneficial for acute inflammation. However, the actual effects of AX on chronic inflammation in adipose tissue (AT) remain unclear. To observe the effects of AX on AT functions in obese mice, we fed six-week-old male C57BL/6J on high-fat-diet (HFD) supplemented with or without 0.02% of AX for 24 weeks. We determined the effect of AX at 10 and 24 weeks of HFD with or without AX on various parameters including insulin sensitivity, glucose tolerance, inflammation, and mitochondrial function in AT. We found that AX significantly reduced oxidative stress and macrophage infiltration into AT, as well as maintaining healthy AT function. Furthermore, AX prevented pathological AT remodeling probably caused by hypoxia in AT. Collectively, AX treatment exerted anti-inflammatory effects via its antioxidant activity in AT, maintained the vascular structure of AT and preserved the stem cells and progenitor's niche, and enhanced anti-inflammatory hypoxia induction factor-2α-dominant hypoxic response. Through these mechanisms of action, it prevented the pathological remodeling of AT and maintained its integrity.

Overview of Anemia; risk factors and solution offering

Objective: The study aims to determine the picture risk factor-related anemia and the solution offered by searching the literature and reviewing it. Method: using literature studies. Article searches using online data-based Science Direct, PubMed, and Google Scholar from 2019 to 2021. They have obtained as many as 20 articles based on inclusion criteria and relevance. Result: Anaemia in young women is still a severe problem among the community. There need to be early detection measures to quickly determine the incidence of anemia and describe anemia as one of the information for all circles young women. Women have a higher risk of anemia, especially young women. This is due to strict dietary habits to prevent weight gain, resulting in malnutrition due to the unmet intake of essential nutrients for the body. Whereas in adolescence, there is an increase in iron demand due to growth and menstruation. Therefore it is very important to provide smart solutions to the incidence of anemia. One that is offered is early detection so that prevention can be done. The use of information technology can be used to conduct early detection of anemia in adolescents because it has been widely utilized among the community, especially adolescents. Conclusion: From the entire literature review, it seems that nutritional status greatly influences the incidence of anemia suffered, and young women are a target for the best intervention. Early detection and use of technology are innovative solutions offered. (AU)

Antenatal care parameters that are the risk factors in the event of preeclampsia in primigravida

Objective: This study aimed to analyze the parameters of antenatal care, which becomes a risk factor against the incidence of preeclampsia in primigravidae in Kolaka. Methods: The study uses case–control studies (case–control), which use a retrospective approach. The population in this study were all primigravida pregnant women recorded in the medical records at the BLUD Hospital. HM Djafar Harun as many as 5796 women and BLUD Benyamin Guluh Hospital as many as 5065 women. The sample in this case group is the primary mother Gravida, who suffered from preeclampsia from January 2014 to September 2018, and the control group was primigravida mothers who did not suffer from preeclampsia in the same period. Results: The results showed that the age of primigravida mothers 14–28 years had a risk of 1.581 times more significant for having preeclampsia than the age group 29–49 years with CI (1.186–2.108), the incidence of hypertension in trimester 1 in primigravida mothers had a risk of 3.405 times greater for preeclampsia than mothers without a history of hypertension in trimester 1 with CI (2.164–5.358), irregular antenatal visits are 1.095 times more likely to develop preeclampsia than regular antenatal visits with CI (0.799–1.539), weight gain primigravida maternal body 1–10 kg 1.540 times greater risk of developing preeclampsia than 10–20 kg of weight gain with CI (1.074–2.207), pregnancy checks according to Antenatal Care non-compliant care standards are 1.333 times more likely to develop preeclampsia than primigravida mothers who obediently do the inspection antenatal care with CI (0.970–1.831). Conclusion: Variables that are very risky with preeclampsia in primigravida mothers based on multivariate analysis are the hypertension incidence in the first trimester with an OR: 3.363 with a CI value of 2.126 and a lower value of 5.318. (AU)

Malnutrition in children associated with low insulin-like growth factor binding protein-3 (IGFBP-3) levels

Objective: This study aimed to compare serum levels of Insulin-like Growth Factor Binding Protein-3 in children with malnutrition and good nutritional status. Method: This cross-sectional study included 41 participants consisting of 31 malnourished, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. IGFBP-3 levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method. Result: Median serum IGFBP-3 levels in malnourished children were found to be lower i.e. 0.35 mcg/mL (minimum–maximum: 0.04–1.52 mcg/mL) compared to well-nourished children 1.52 ng/mL (minimum–maximum 0.47–3.17 mcg/mL). Conclusion: Serum IGFBP-3 levels can be used as indicators to assess nutritional status. (AU)

Leptin levels in children with malnutrition

Objective: This study aimed at comparing serum levels of leptin in children with malnutrition and good nutritional status. Method: This cross-sectional study included 41 participants consisting of 31 malnutrition, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. Leptin levels were determined by ELISA (Enzyme-Linked Immunosorbent Assay) method. Results: Median serum leptin level for malnutrition children were found to be lower, i.e., 9.23 (6.02–197.2) ng/mL compared to well-nourished children 30.95 (6.02–89.36) ng/mL. Conclusion: Serum leptin levels can be used as indicators to assess nutritional status. (AU)

Determinant of anemia in pregnancy at Polewali Mandar District, South Sulawesi, Indonesia

Objectives: The study was aimed to determine the influence of the determinant of anemia in pregnancy in the district Polewali Mandar, Indonesia. Methods: This study uses a cross-sectional design analysis. The subject in this study was the third-trimester pregnant mother with a sample amount of 80 people selected using the cluster sampling technique. Results: The majority of this study showed that as much as 93.8% of the third-trimester pregnant women were suffering from anemia, and 6.8% of the third-trimester pregnant women were not subjected to anemia. Based on statistical test results using the Chi-Square test obtained that age (P-value = 0.644), education (P-value = 0.003), economic Status (P-value = 0.138), Antenatal care visit (P-value = 0.584), nutritional Status (P-value = 0.929), parity (P-value = 0.380), Pregnancy distance (P-value = 0.776), consumption of iron tablets (P-value = 0.036) and worm infections (P-value = 0.821). Results showed that two determinants significantly affect anemia in pregnancy, and seven determinants did not significantly affect anemia in pregnancy Regency of Polewali Mandar. Conclusion: A significantly related determinant in the study is the education and consumption of iron tablets. (AU)

Malnutrition in children associated with low growth hormone (Gh) Levels

Objective: This study aimed to compare serum levels of Growth Hormone in children with malnutrition and good nutritional status. Method: This cross-sectional study included 41 participants consisting of 31 malnourished, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. GH levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method. Result: Median serum GH levels in malnourished children were found to be lower i.e. 1.25 ng/mL (minimum–maximum: 0.10–6.19 ng/mL) compared to well-nourished children 11.01 ng/mL (1.72–15.64 ng/mL). Conclusion: Serum GH levels can be used as indicators to assess nutritional status. (AU)

Long-Term Ketogenic Diet Induces Metabolic Acidosis, Anemia, and Oxidative Stress in Healthy Wistar Rats.

BACKGROUND: Ketogenic diet has been used as supportive therapy in a range of conditions including epilepsy, diabetes mellitus, and cancer. OBJECTIVE: This study aimed to investigate the effects of long-term consumption of ketogenic diet on blood gas, hematological profiles, organ functions, and superoxide dismutase level in a rat model. MATERIALS AND METHODS: Fifteen male Wistar rats were divided into control (n = 8) and ketogenic (n = 7) groups. Controls received standard diet contained 52.20% of carbohydrates, 7.00% fat, and 15.25% protein; meanwhile, the ketogenic group received a high-fat-low-carbohydrate diet which contained 5.66% of carbohydrate, 86.19% fat, and 8.15% protein. All rats were caged individually and received 30g of either standard or high-fat-low-carbohydrate pellets. The experiment was carried out for 60 days before the blood samples were taken and analyzed to obtain blood gas, cell counts, organ biomarkers, and plasma antioxidant superoxide dismutase (SOD) levels. RESULTS: The rats subjected to ketogenic diet experienced a marked decrease in body weight, blood sugar, and increased blood ketones (p < 0.05). The average blood pH was 7.36 ± 0.02 and base excess was -5.57 ± 2.39 mOsm/L, which were significantly lower than controls (p < 0.05). Hematological analysis showed significantly lower erythrocyte, hemoglobin, and hematocrit levels. No significant changes were found in alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels, indicating normal liver and kidney functions. Nevertheless, plasma SOD level significantly reduced with ketogenic diet. CONCLUSION: Long-term ketogenic diet induces metabolic acidosis, anemia, and reduced antioxidant enzyme level in rats following 60 days of consuming high-fat-low-carbohydrate diet.

CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors.

Adipose tissue resident macrophages have important roles in the maintenance of tissue homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory cytokines. Here, we show that M2-like macrophages in adipose tissue regulate systemic glucose homeostasis by inhibiting adipocyte progenitor proliferation via the CD206/TGFß signaling pathway. We show that adipose tissue CD206+ cells are primarily M2-like macrophages, and ablation of CD206+ M2-like macrophages improves systemic insulin sensitivity, which was associated with an increased number of smaller adipocytes. Mice genetically engineered to have reduced numbers of CD206+ M2-like macrophages show a down-regulation of TGFß signaling in adipose tissue, together with up-regulated proliferation and differentiation of adipocyte progenitors. Our findings indicate that CD206+ M2-like macrophages in adipose tissues create a microenvironment that inhibits growth and differentiation of adipocyte progenitors and, thereby, control adiposity and systemic insulin sensitivity.Adipose tissue contains macrophages that can influence both local and systemic metabolism via the secretion of cytokines. Here, Nawaz et al. report that M2-like macrophages, present in adipose tissue, create a microenvironment that inhibits proliferation of adipocyte progenitors due to the secretion of TGF-ß1.

HIF-1α in Myeloid Cells Promotes Adipose Tissue Remodeling Toward Insulin Resistance.

Adipose tissue hypoxia is an important feature of pathological adipose tissue expansion. Hypoxia-inducible factor-1α (HIF-1α) in adipocytes reportedly induces oxidative stress and fibrosis, rather than neoangiogenesis via vascular endothelial growth factor (VEGF)-A. We previously reported that macrophages in crown-like structures (CLSs) are both hypoxic and inflammatory. In the current study, we examined how macrophage HIF-1α is involved in high-fat diet (HFD)-induced inflammation, neovascularization, hypoxia, and insulin resistance using mice with myeloid cell-specific HIF-1α deletion that were fed an HFD. Myeloid cell-specific HIF-1α gene deletion protected against HFD-induced inflammation, CLS formation, poor vasculature development in the adipose tissue, and systemic insulin resistance. Despite a reduced expression of Vegfa in epididymal white adipose tissue (eWAT), the preadipocytes and endothelial cells of HIF-1α-deficient mice expressed higher levels of angiogenic factors, including Vegfa, Angpt1, Fgf1, and Fgf10 in accordance with preferable eWAT remodeling. Our in vitro study revealed that lipopolysaccharide-treated bone marrow-derived macrophages directly inhibited the expression of angiogenic factors in 3T3-L1 preadipocytes. Thus, macrophage HIF-1α is involved not only in the formation of CLSs, further enhancing the inflammatory responses, but also in the inhibition of neoangiogenesis in preadipocytes. We concluded that these two pathways contribute to the obesity-related physiology of pathological adipose tissue expansion, thus causing systemic insulin resistance.

Telmisartan improves insulin resistance and modulates adipose tissue macrophage polarization in high-fat-fed mice.

Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-γ agonist, reportedly has more beneficial effects on insulin sensitivity than other angiotensin II type 1 receptor blockers. In this study, we studied the effects of telmisartan on the adipose tissue macrophage phenotype in high-fat-fed mice. Telmisartan was administered for 5 wk to high-fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in visceral adipose tissues were then examined. An insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight, and adipocyte size without affecting the amount of energy intake. Telmisartan reduced the mRNA expression of CD11c and TNF-α, M1 macrophage markers, and significantly increased the expressions of M2 markers, such as CD163, CD209, and macrophage galactose N-acetyl-galactosamine specific lectin (Mgl2), in a quantitative RT-PCR analysis. A flow cytometry analysis showed that telmisartan decreased the number of M1 macrophages in visceral adipose tissues. In conclusion, telmisartan improves insulin sensitivity and modulates adipose tissue macrophage polarization to an antiinflammatory M2 state in high-fat-fed mice.