The buckwheat iminosugar D-fagomine attenuates sucrose-induced steatosis and hypertension in rats

AbstractD-Fagomine (1,2 dideoxynojirimycin) is an iminosugar, a carbohydrate analogue that includes an endocyclic nitrogen instead of oxygen, that is naturally present in buckwheat and buckwheat-based foodstuffs. This study examines the long-term functional effect of d-fagomine on sucrose-induced factors of metabolic syndrome and explores possible molecular mechanisms behind its action. We evaluated Wistar Kyoto rats fed a standard diet were given a 35% sucrose (glucose/fructose) solution with d-fagomine (or not, for comparison) or mineral water (controls) for 24 weeks. The variables measured were body weight and energy intake; glucose tolerance (oral glucose tolerance test); plasma leptin concentration; plasma lipid profile; the populations of Bacteroidetes, Firmicutes, bacteroidales, clostridiales, enterobacteriales, and Escherichia coli in feces; blood pressure; urine uric acid and F2t isoprostanes (F2-IsoPs); perigonadal fat deposition and hepatic histology and diacylglycerols (DAGs) in liver and adipose tissue. We found that d-Fagomine reduced sucrose induced hypertension, urine uric acid, F2-IsoPs as markers of oxidative stress (OS), steatosis and liver DAGs (32:1, 32:2, 34:1 and 36:2) without affecting perigonadal (visceral) fat deposition or DAG levels in visceral adipose tissue. It showed a slight tendency to reduce sugar induced impaired glucose tolerance. d-Fagomine also promoted excretion of enterobacteriales generated by the dietary intervention. We postulate that fructose increases visceral fat deposition independently of liver de novo liposynthesis and that d-fagomine attenuates steatosis and blood pressure mainly by reducing liver fructose levels. The reduction of blood pressure may be associated with an effect on uric acid synthesis while the reduced levels of selected active liver DAGs may explain the weak effect on sucrose-induced impaired glucose tolerance, which may be primarily induced by visceral fat deposition. In conclusion, the increased populations of excreted enterobacteriales may be connected to the levels of excreted uric acid. d-Fagomine counteracts sucrose-induced steatosis and hypertension presumably by reducing the postprandial levels of fructose in the liver as a consequence of intestinal sucrase inhibition.

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Subcutaneous Adipose Tissue Cell-derived Cytokines Are Early Markers of Impaired Glucose Tolerance in Severe Obesity

10.21203/rs.3.rs-123645/v1 ◽

2021 ◽

Author(s):

Vittoria D'Esposito ◽

Maria Rosaria Ambrosio ◽

Domenico Liguoro ◽

Giuseppe Perruolo ◽

Manuela Lecce ◽

...

Keyword(s):

Adipose Tissue ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Severe Obesity ◽

Serum Levels ◽

Tolerance Test ◽

Tissue Cell ◽

Oral Glucose ◽

Mrna Levels

Abstract Background Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. Methods 92 severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an Oral Glucose Tolerance Test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or Type 2 Diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and Mesenchymal Stem Cells (MSCs) were isolated, characterized and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines and growth factors were assessed by multiplex ELISA. Results Serum levels of IL-9, IL-13 and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were 3-fold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein, were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT–derived MSCs to quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. Conclusion In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and may be, at least in part, attenuated by quercetin.

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Ayurvedic Herbal Preparation Supplementation Does Not Improve Metabolic Health in Impaired Glucose Tolerance Subjects; Observations from a Randomised Placebo Controlled Trial

Nutrients ◽

10.3390/nu13010260 ◽

2021 ◽

Vol 13 (1) ◽

pp. 260

Author(s):

Diederik Esser ◽

Juri Matualatupauw ◽

Ric C. H. de Vos ◽

Ron Wehrens ◽

Jos van der Stappen ◽

...

Keyword(s):

Blood Pressure ◽

Adipose Tissue ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Augmentation Index ◽

Controlled Trial ◽

Herbal Preparation ◽

Plant Metabolites ◽

Double Blind ◽

Potential Health

The increased usage of alternative Ayurvedic treatments as potential health-beneficial therapies emphasizes the importance of studying its efficacy in sound placebo-controlled intervention trials. An example of such a traditional Ayurvedic herbal preparation is Mohana Choorna, a mixture composed of 20 different herbs and used to prevent and treat type 2-diabetes (T2D). We studied the efficacy of “Mohana Choorna” on T2D-related parameters in subjects with impaired glucose tolerance. In a double blind, placebo-controlled cross-over trial, 19 overweight (BMI > 27 kg/m2) subjects aged 50–70 years with an impaired glucose tolerance received two four-week interventions, i.e., herbal or placebo with a four-week wash-out between interventions. HbA1c, glucose, insulin, triglycerides, cholesterol, blood pressure and augmentation index were measured before and after both interventions at fasting and during a glucose tolerance test. After both interventions, urine was collected to measure treatment exposure using LCMS-based metabolomics and whole genome gene-expression in adipose tissue of 13 subjects. The herbal intervention did not affect plasma glucose triglycerides, cholesterol, blood pressure or the augmentation index but showed a trend towards an increased insulin, HOMA-IR and postprandial insulin levels (p = 0.054, p = 0.056 and p = 0.095 respectively). An increase in expression of inflammation-related gene sets in adipose tissue was observed after the herbal intervention compared to placebo. Urine metabolomic analysis did not reveal a correlation of the presence of specific plant metabolites with “health markers”. Our findings suggest that there is no substantiating evidence to claim that four weeks’ use of the Ayurvedic herbal supplement Mohana Choorna beneficially affects glucose homeostasis.

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Hibiscus sabdariffa ethanolic extract modulates adipokine levels, decreases visceral fat and improves glycemic profile in high-fat/sugar diet-induced obese rats

Nutrition & Food Science ◽

10.1108/nfs-03-2020-0092 ◽

2020 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Karla E. Von Dentz ◽

Bianca S. Silva ◽

Eveline A.I.F. Queiroz ◽

Gisele F. Bomfim ◽

André F. Nascimento ◽

...

Keyword(s):

Adipose Tissue ◽

Glucose Tolerance ◽

Visceral Fat ◽

Ethanolic Extract ◽

Oral Glucose ◽

Hibiscus Sabdariffa ◽

High Fat ◽

Content Type ◽

Protein Levels ◽

Obese Rats

Purpose The purpose of this study is to evaluate the effect of Hibiscus sabdariffa ethanolic extract (HsE) on protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, adiponectin and leptin in adipose tissue, as well as on the lipid and glycemic profiles of high-fat/sugar diet-induced obese (DIO) rats. Design/methodology/approach Obesity was induced in male Wistar rats through a high-fat/sugar diet provided for eight weeks. Control rats received a standard diet. The high-fat/sugar DIO animals were subsequently randomized into DIO (n = 8) and DIO treated with HsE (DIO + HsE, n = 8, 150 mg/kg/day) by gavage, for additional eight weeks. Oral glucose tolerance test was performed, and blood samples and epididymal adipose tissue were collected for biochemical analysis and adipokine protein level evaluation, respectively. Findings Compared to the DIO rats, HsE treatment decreased weight gain (50.6%) and mesenteric fat (42%), indicated as diminished visceral fat (22.5%). HsE did not affect the lipid profile and TNF-α levels in adipose tissue; however, it effectively prevented a 13% increase in fasting glucose levels and improved glucose tolerance. Compared with the C group, HsE normalized the adiponectin levels and leptin/adiponectin ratio and decreased the IL-6 (55%) and leptin (18.6%) levels in adipose tissue of obese rats. Originality/value HsE improves adipokine protein levels in high-fat/sugar DIO rats, demonstrating the clinical efficacy of HsE in the treatment of obesity and obesity-related diseases.

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High predictability of impaired glucose tolerance by combining cardiometabolic screening parameters in obese children

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0289 ◽

2017 ◽

Vol 30 (2) ◽

Author(s):

Cornelis Jan de Groot ◽

Jeroen van der Grond ◽

Yosine Delgado ◽

Edmond H.H.M. Rings ◽

Sabine E. Hannema ◽

...

Keyword(s):

Blood Pressure ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Liver Enzymes ◽

Elevated Blood Pressure ◽

Oral Glucose ◽

Elevated Blood ◽

Obese Children ◽

Number Needed To Screen ◽

Elevated Liver Enzymes

AbstractBackground:There is debate on which overweight and obese children should be screened for the presence of impaired glucose tolerance (IGT) by oral glucose tolerance testing (OGTT). The objective of the study was to identify risk factors predictive of the presence of IGT.Methods:In a cohort of overweight children, who underwent OGTT, we determined the association of anthropometric and laboratory parameters with IGT and whether combining parameters improved the sensitivity of screening for IGT.Results:Out of 145 patients, IGT was present in 11, of whom two had impaired fasting glucose (IFG). Elevated blood pressure (p=0.025) and elevated liver enzymes (p=0.003) were associated with IGT, whereas IFG was not (p=0.067), screening patients with either one of these parameters predicted IGT with a high sensitivity of 1.00, and a number needed to screen of 5.7.Conclusions:Screening all patients with either IFG, presence of elevated blood pressure and elevated liver enzymes, significantly increases predictability of IGT compared to using IFG alone.

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ILC2s Improve Glucose Metabolism Through the Control of Saturated Fatty Acid Absorption Within Visceral Fat

Frontiers in Immunology ◽

10.3389/fimmu.2021.669629 ◽

2021 ◽

Vol 12 ◽

Author(s):

Takuro Okamura ◽

Yoshitaka Hashimoto ◽

Jun Mori ◽

Mihoko Yamaguchi ◽

Saori Majima ◽

...

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Chronic Inflammation ◽

Saturated Fatty Acid ◽

Visceral Fat ◽

Saturated Fatty Acids ◽

Fatty Acid Absorption

Background and aimsGroup 2 innate lymphoid cells (ILC2s) have been implicated in the regulation of metabolic homeostasis in mice.MethodsIn this study, the role of ILC2s in white adipose tissue (WAT) was investigated using ST2, an IL-33 receptor that is expressed on ILC2 knockout mice.ResultsThe deficiency of ST2 decreased ILC2s in WAT, whereas ex-ILC2, which acquired group 1 innate lymphoid cell (ILC1)-like traits, was increased. This led to significant metabolic disorders such as visceral fat obesity, decreased browning in WAT, reduction of energy metabolism, and impaired glucose tolerance, compared to wild type (WT) mice. Those metabolic abnormalities of ST2-knockout (ST2KO) mice were not ameliorated by IL-33 administration, but impaired glucose tolerance and visceral fat obesity were significantly improved by transplantation of ILCs from the bone marrow of WT mice. The relative expression of Cd36 in WAT increased due to the deficiency of ST2, and the storage of saturated fatty acids in WAT of ST2KO mice was significantly higher than that of WT mice. Moreover, saturated fatty acids aggravated the chronic inflammation in adipocytes, promoted the differentiation of M1-like macrophages, and inhibited that of M2-like macrophages.ConclusionsOur results indicated that ILC2 regulates diet-induced obesity and chronic inflammation through the regulation of saturated fatty acid absorption in visceral adipose tissue.

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Visceral Fat Accumulation Is Associated With Circadian Blood Pressure in Japanese Patients With Impaired Glucose Tolerance

Diabetes Care ◽

10.2337/dc10-2258 ◽

2011 ◽

Vol 34 (3) ◽

pp. e32-e32 ◽

Cited By ~ 4

Author(s):

T. Masaki ◽

F. Anan ◽

H. Yoshimatsu

Keyword(s):

Blood Pressure ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Visceral Fat ◽

Japanese Patients ◽

Fat Accumulation ◽

Visceral Fat Accumulation ◽

Circadian Blood Pressure

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The size of the loading dose as an important determinant of the results of the oral glucose tolerance test: a study in subjects with slightly impaired glucose tolerance

Diabetes ◽

10.2337/diabetes.27.1.42 ◽

1978 ◽

Vol 27 (1) ◽

pp. 42-48 ◽

Cited By ~ 10

Author(s):

E. de Nobel ◽

A. van't Laar

Keyword(s):

Glucose Tolerance ◽

Oral Glucose Tolerance Test ◽

Impaired Glucose Tolerance ◽

Glucose Tolerance Test ◽

Important Determinant ◽

Tolerance Test ◽

Oral Glucose ◽

Loading Dose ◽

Oral Glucose Tolerance

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QOL-43. ENDOCRINE AND METABOLIC CHANGES IN CHILDREN TREATED FOR MEDULLOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa222.700 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii439-iii439

Author(s):

Alexey Kalinin ◽

Natalia Strebkova ◽

Olga Zheludkova

Keyword(s):

Insulin Resistance ◽

Body Composition ◽

Glucose Tolerance ◽

Oral Glucose Tolerance Test ◽

Impaired Glucose Tolerance ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Hormone Deficiency ◽

Oral Glucose ◽

Oral Glucose Tolerance

Abstract We examined 63 patients (40 males/23 females) after complex treatment of medulloblastoma. Patients had a median age (range) of 11.3 (5.5 ÷ 17.9) years. The median time after the end of treatment was 3.7 (1.5 ÷ 11.6) years. Endocrine disorders were detected with the following frequency: growth hormone deficiency - 98.41% (62 of 63 patients), thyroid hormone deficiency – 69.8% (44/63), adrenal hormone deficiency - 17.4% (11/63). Three cases (4.7%) of premature sexual development were also detected. Lipids levels, beta-cell function and insulin resistance (IR) during 2-h oral glucose tolerance test were evaluated. A mono frequent bioelectrical impedanciometer was used to measure body composition. Overweight (SDS BMI> 1) was observed only in 16 patients (3 girls and 13 boys), obesity (SDS BMI> 2) in 1 boy. Dyslipidemia was found in 34 patients (54%). All patients underwent oral glucose tolerance test. Insulin resistance (ISI Matsuda <2.5 and/or HOMA-IR> 3.2) was detected in 7 patients (11/1%), impaired glucose tolerance (120 min glucose ≥7.8 mmol / l) was observed in 2 patients with IR and in 2 patients without IR. At the same time, IR and impaired glucose tolerance were encountered in only 5 children with overweight and no one with obesity. All patients with impaired glucose tolerance had normal values of fasting glucose (4.3 ÷ 5.04 mmol / l) and HbA1c (4.8 ÷ 5.8%). A bioelectrical impedanciometer was used to measure body composition in 49 cases, the percentage of adipose tissue was increased in 14 patients (28%) with normal BMI.

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