Diabetogenic diet-induced insulin resistance associates with lipid droplet proteins and adipose tissue secretome, but not with sexual dimorphic adipose tissue fat accumulation in Wistar rats

In the present study, we aimed to investigate whether chronic oral glutamine (Gln) supplementation may alter metabolic parameters and the inflammatory profile in overweight and obese humans as well as whether Gln may modulate molecular pathways in key tissues linked to the insulin action in rats. Thirty-nine overweight/obese volunteers received 30 g of Gln or alanine (Ala-control) for 14 days. Body weight (BW), waist circumference (WC), hormones, and pro-inflammatory markers were evaluated. To investigate molecular mechanisms, Gln or Ala was given to Wistar rats on a high-fat diet (HFD), and metabolic parameters, euglycemic hyperinsulinemic clamp with tracers, and Western blot were done. Gln reduced WC and serum lipopolysaccharide (LPS) in overweight volunteers. In the obese group, Gln diminished WC and serum insulin. There was a positive correlation between the reduction on WC and LPS. In rats on HFD, Gln reduced adiposity, improved insulin action and signaling, and reversed both defects in glucose metabolism in the liver and muscle. Gln supplementation increased muscle glucose uptake and reversed the increased hepatic glucose production, in parallel with a reduced glucose uptake in adipose tissue. This insulin resistance in AT was accompanied by enhanced IRS1 O-linked-glycosamine association in this tissue, but not in the liver and muscle. These data suggest that Gln supplementation leads to insulin resistance specifically in adipose tissue via the hexosamine pathway and reduces adipose mass, which is associated with improvement in the systemic insulin action. Thus, further investigation with Gln supplementation should be performed for longer periods in humans before prescribing as a beneficial therapeutic approach for individuals who are overweight and obese.

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Urtica dioica Whole Vegetable as a Functional Food Targeting Fat Accumulation and Insulin Resistance-a Preliminary Study in a Mouse Pre-Diabetic Model

Nutrients ◽

10.3390/nu12041059 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1059

Author(s):

Si Fan ◽

Samnhita Raychaudhuri ◽

Olivia Kraus ◽

Md Shahinozzaman ◽

Leila Lofti ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Glucose Metabolism ◽

High Fat Diet ◽

Urtica Dioica ◽

Whole Body ◽

High Fat ◽

Fat Accumulation ◽

Diet Induced Obesity

The shoot of Urtica dioica is used in several cultures as a vegetable or herb. However, not much has been studied about the potential of this plant when consumed as a whole food/vegetable rather than an extract for dietary supplements. In a 12-week dietary intervention study, we tested the effect of U. dioica vegetable on high fat diet induced obesity and insulin resistance in C57BL/6J mice. Mice were fed ad libitum with isocaloric diets containing 10% fat or 45% fat with or without U. dioica. The diet supplemented with U. dioica attenuated high fat diet induced weight gain (p < 0.005; n = 9), fat accumulation in adipose tissue (p < 0.005; n = 9), and whole-body insulin resistance (HOMA-IR index) (p < 0.001; n = 9). Analysis of gene expression in skeletal muscle showed no effect on the constituents of the insulin signaling pathway (AKT, IRS proteins, PI3K, GLUT4, and insulin receptor). Notable genes that impact lipid or glucose metabolism and whose expression was changed by U. dioica include fasting induced adipocyte factor (FIAF) in adipose and skeletal muscle, peroxisome proliferator-activated receptor-α (Ppar-α) and forkhead box protein (FOXO1) in muscle and liver, and Carnitine palmitoyltransferase I (Cpt1) in liver (p < 0.01). We conclude that U. dioica vegetable protects against diet induced obesity through mechanisms involving lipid accumulation and glucose metabolism in skeletal muscle, liver, and adipose tissue.

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Abstract 220: Exercise Training Attenuates Hypertension and Insulin Resistance in Old Fructose-fed Ovariectomized Rats

Hypertension ◽

10.1161/hyp.62.suppl_1.a220 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Jacqueline F Machi ◽

Nathalia Bernardes ◽

Daniele S Dias ◽

Ivana C Moraes-Silva ◽

Fernando Dos Santos ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Adipose Tissue ◽

Exercise Training ◽

Wistar Rats ◽

Physical Capacity ◽

Ovariectomized Rats ◽

Ovarian Hormone ◽

Female Wistar Rats ◽

Hormone Deprivation

Menopause and aging are associated with a gradual increase in systolic blood pressure. Poor eating habits through food containing fructose, have also been related to alterations in the cardiovascular system; however, there are few studies available in the literature relating exercise training (ET), menopause, aging and metabolic syndrome. The aim of the present study was to investigate the effects of ET in ovarian hormone deprivation and/or fructose consumption in old Wistar rats. Female Wistar rats (24 months old) were ovariectomized, fed with fructose (100g/L in drinking water) or normal water, and submitted to an ET protocol in treadmill (1 h/day; 5 days/wk for 8 wk, ~ 40-60% of maximum test) or kept sedentary. The groups were: ovariectomized (O, n= 8), ovariectomized trained (OT, n= 8), ovariectomized fructose (OF, n= 8) and ovariectomized fructose trained (OFT, n= 8). Glycemia, triglycerides, adipose tissue, insulin resistance, physical capacity and blood pressure (BP) were evaluated at the end of the protocol. While the glycemia values remained within the normal range (O:90.1±7.; OT:85.2±2; OF:86±2; OFT:80.6±3 mg/dl) and the triglycerides values were increased in OF group (OF:182±20 vs. O:140.3±9; OT:143.5±7;; OFT:140 ±12 mg/dl). The physical capacity was increased in both OFT (1.8±0.1 Km/h) and OF (1.6±0.07 Km/h) when compared with sedentary peers (O:1.1±0.05; OF: 1.1±0.05 Km/h). The metabolic results showed that ET decreased the adipose tissue in (OT: 6.7±0.9 and OFT: 5.28±0.6 vs. OF: 10.07±0.6 g), and insulin resistance (OT:4.8±0.2 and OFT: 5.0±0.2 vs. OF: 3.2±0.6 mg/dl/%). No differences were observed in O group (O: 6.5±0.8g and 4.5±0.2 mg/dl/min). Finally, ET attenuated the increase in mean BP in both OT and OFT rats (O:119±2; OT 110±2; OF:119±2; OFT: 107±1 mmHg). The same behavior was observed in systolic BP (O:142±2; OT 127±2; OF:143±2; OFT: 129±1 mmHg) and diastolic BP (O:100±2; OT 92±2; OF:98±2; OFT: 89±1 mmHg). In conclusion, low to moderate aerobic ET can attenuate the deleterious effects of ovarian hormone deprivation, and/or fructose consumption, especially the blood pressure increase in old female Wistar rats.

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Thirty days of combined consumption of high-fat diet and fructose-rich beverages promotes insulin resistance and modulates inflammatory response and histomorphometry parameters of liver, pancreas, and adipose tissue in Wistar rats

Nutrition ◽

10.1016/j.nut.2021.111403 ◽

2021 ◽

pp. 111403

Author(s):

MELO BP ◽

ZACARIAS AC ◽

OLIVEIRA JCC ◽

DE SOUZA CORDEIRO LM ◽

SABINO J ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Inflammatory Response ◽

High Fat Diet ◽

Wistar Rats ◽

High Fat

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Phenotypical heterogeneity linked to adipose tissue dysfunction in patients with Type 2 diabetes

Clinical Science ◽

10.1042/cs20160348 ◽

2016 ◽

Vol 130 (19) ◽

pp. 1753-1762 ◽

Cited By ~ 11

Author(s):

Ilaria Barchetta ◽

Francesco Angelico ◽

Maria Del Ben ◽

Michele Di Martino ◽

Flavia Agata Cimini ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Insulin Secretion ◽

Fat Deposition ◽

Metabolic Phenotype ◽

Ectopic Fat ◽

Model Assessment ◽

Fat Accumulation

Adipose tissue (AT) inflammation leads to increased free fatty acid (FFA) efflux and ectopic fat deposition, but whether AT dysfunction drives selective fat accumulation in specific sites remains unknown. The aim of the present study was to investigate the correlation between AT dysfunction, hepatic/pancreatic fat fraction (HFF, PFF) and the associated metabolic phenotype in patients with Type 2 diabetes (T2D). Sixty-five consecutive T2D patients were recruited at the Diabetes Centre of Sapienza University, Rome, Italy. The study population underwent clinical examination and blood sampling for routine biochemistry and calculation of insulin secretion [homoeostasis model assessment of insulin secretion (HOMA-β%)] and insulin-resistance [homoeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (ADIPO-IR)] indexes. Subcutaneous (SAT) and visceral (VAT) AT area, HFF and PFF were determined by magnetic resonance. Some 55.4% of T2D patients had non-alcoholic fatty liver disease (NAFLD); they were significantly younger and more insulin-resistant than non-NAFLD subjects. ADIPO-IR was the main determinant of HFF independently of age, sex, HOMA-IR, VAT, SAT and predicted severe NAFLD with the area under the receiver operating characteristic curve (AUROC)=0.796 (95% confidence interval: 0.65–0.94, P=0.001). PFF was independently associated with increased total adiposity but did not correlate with AT dysfunction, insulin resistance and secretion or NAFLD. The ADIPO-IR index was capable of predicting NAFLD independently of all confounders, whereas it did not seem to be related to intrapancreatic fat deposition; unlike HFF, higher PFF was not associated with relevant alterations in the metabolic profile. In conclusion, the presence and severity of AT dysfunction may drive ectopic fat accumulation towards specific targets, such as VAT and liver, therefore evaluation of AT dysfunction may contribute to the identification of different risk profiles among T2D patients.

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Fatty Liver Has Stronger Association With Insulin Resistance Than Visceral Fat Accumulation in Nonobese Japanese Men

Journal of the Endocrine Society ◽

10.1210/js.2019-00052 ◽

2019 ◽

Vol 3 (7) ◽

pp. 1409-1416 ◽

Cited By ~ 7

Author(s):

Satoshi Kadowaki ◽

Yoshifumi Tamura ◽

Yuki Someya ◽

Kageumi Takeno ◽

Hideyoshi Kaga ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Fatty Liver ◽

Visceral Fat ◽

Visceral Fat Area ◽

Japanese Men ◽

Fat Accumulation ◽

Visceral Fat Accumulation ◽

Intrahepatic Lipid

Abstract Context Asians have a high prevalence of insulin resistance, even in the nonobese state. Whereas both visceral fat accumulation (VFA) and fatty liver (FL) have been shown to be associated with insulin resistance, it is still unclear which is a better marker to predict insulin resistance in nonobese Asians. Objective The aim of this study was to investigate the relation between VFA or FL and insulin resistance in nondiabetic nonobese Japanese men who do not have diabetes. Design and Participants We studied 87 nonobese (body mass index <25 kg/m2) Japanese men without diabetes. Using a two-step hyperinsulinemic euglycemic clamp, we evaluated insulin sensitivity in adipose tissue, muscle, and liver. Intrahepatic lipid and abdominal visceral fat area were measured by 1H-magnetic resonance spectroscopy and MRI, respectively. Subjects were divided into four groups based on the presence or absence of VFA (visceral fat area ≥100 cm2) and FL (intrahepatic lipid ≥ 5%): control (non-VFA, non-FL; n = 54), VFA only (n = 18), FL only (n = 7), and VFA plus FL (n = 8). Results Subjects in the FL only and VFA plus FL groups had insulin resistance in adipose tissue and muscle, as well as relatively lower hepatic insulin sensitivity. The specific insulin sensitivities in these organs were comparable in the VFA only and control groups. Conclusions In nonobese Japanese men without diabetes, subjects with FL only or VFA plus FL but not VFA only had insulin resistance, suggesting that FL may be a more useful clinical marker than VFA to predict insulin resistance in nonobese Japanese men without diabetes.

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Quercetin can reduce insulin resistance without decreasing adipose tissue and skeletal muscle fat accumulation

Genes & Nutrition ◽

10.1007/s12263-013-0361-7 ◽

2013 ◽

Vol 9 (1) ◽

Cited By ~ 34

Author(s):

N. Arias ◽

M. T. Macarulla ◽

L. Aguirre ◽

M. G. Martínez-Castaño ◽

M. P. Portillo

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Fat Accumulation ◽

Reduce Insulin Resistance

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Olive Leaf Extract Supplementation to Old Wistar Rats Attenuates Aging-Induced Sarcopenia and Increases Insulin Sensitivity in Adipose Tissue and Skeletal Muscle

Antioxidants ◽

10.3390/antiox10050737 ◽

2021 ◽

Vol 10 (5) ◽

pp. 737

Author(s):

Daniel González-Hedström ◽

Teresa Priego ◽

Sara Amor ◽

María de la Fuente-Fernández ◽

Ana Isabel Martín ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Brown Adipose Tissue ◽

Wistar Rats ◽

Leaf Extract ◽

Olive Leaf ◽

Olive Leaf Extract ◽

Brown Adipose

Aging is associated with increased visceral adiposity and a decrease in the amount of brown adipose tissue and muscle mass, known as sarcopenia, which results in the development of metabolic alterations such as insulin resistance. In this study, we aimed to analyze whether 3-week supplementation with a phenolic-rich olive leaf extract (OLE) to 24 months-old male Wistar rats orally (100 mg/kg) attenuated the aging-induced alterations in body composition and insulin resistance. OLE treatment increased brown adipose tissue and attenuated the aging-induced decrease in protein content and gastrocnemius weight. Treatment with OLE prevented the aging-induced increase in the expression of PPAR-γ in visceral and brown adipose tissues, while it significantly increased the expression of PPAR-α in the gastrocnemius of old rats and reduced various markers related to sarcopenia such as myostatin, HDAC-4, myogenin and MyoD. OLE supplementation increased insulin sensitivity in explants of gastrocnemius and epididymal visceral adipose tissue from aged rats through a greater activation of the PI3K/Akt pathway, probably through the attenuation of inflammation in both tissues. In conclusion, supplementation with OLE prevents the loss of muscle mass associated with aging and exerts anti-inflammatory and insulin-sensitizing effects on adipose tissue and skeletal muscle.

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Lipasin/Betatrophin Is Differentially Expressed in Liver and White Adipose Tissue Without Association With Insulin Resistance in Wistar and Goto-Kakizaki Rats

Physiological Research ◽

10.33549/physiolres.933339 ◽

2017 ◽

pp. 273-281

Author(s):

M. CAHOVÁ ◽

D. HABART ◽

T. OLEJÁR ◽

Z. BERKOVÁ ◽

Z. PAPÁČKOVÁ ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Wistar Rats ◽

Gk Rats ◽

Peripheral Insulin Resistance ◽

Age Related ◽

Hepatic Triacylglycerol

Lipasin is a recently identified lipokine expressed predominantly in liver and in adipose tissue. It was linked to insulin resistance in mice and to type 1 and type 2 diabetes (T1D, T2D) in humans. No metabolic studies concerning lipasin were performed yet in rats. Therefore, we used rat model of T2D and insulin resistance, Goto-Kakizaki (GK) rats, to determine changes of lipasin expression in liver and in white adipose tissue (WAT) over 52 weeks in the relation to glucose tolerance, peripheral tissue insulin sensitivity and adiposity. GK rats were grossly glucose intolerant since the age of 6 weeks and developed peripheral insulin resistance at the age of 20 weeks. Expression of lipasin in the liver did not differ between GK and Wistar rats, declining with age, and it was not related to hepatic triacylglycerol content. In WAT, the lipasin expression was significantly higher in Wistar rats where it correlated positively with adiposity. No such correlation was found in GK rats. In conclusion, lipasin expression was associated neither with a mild age-related insulin resistance (Wistar), nor with severe genetically-based insulin resistance (GK).

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