The effect of aerobic, resistance, and combined training on PPAR-α, SIRT1 gene expression, and insulin resistance in high-fat diet-induced NAFLD male rats

Obesity is the result of an expansion and increase in the number of individual adipocytes. Since changes in gene expression during adipocyte differentiation and hypertrophy are closely associated with insulin resistance and cardiovascular diseases, further insight into the molecular basis of obesity is needed to better understand obesity-associated diseases. MicroRNAs (miRNAs) are approximately 17–24nt single stranded RNA, that post-transcriptionally regulate gene expression. MiRNAs control cell growth, differentiation and metabolism, and may be also involved in pathogenesis and pathophysiology of diseases. It has been proposed that miR-143 plays a role in the differentiation of preadipocytes into mature adipocytes in culture. However, regulated expression of miR-143 in the adult adipose tissue during the development of obesity in vivo is unknown. To solve this problem, C57BL/6 mice were fed with either high-fat diet (HFD) or normal chow (NC). Eight weeks later, severe insulin resistance was observed in mice on HFD. Body weight increased by 35% and the mesenteric fat weight increased by 3.3-fold in HFD mice compared with NC mice. We measured expression levels of miR-143 in the mesenteric fat tissue by real-time PCR and normalized with those of 5S ribosomal RNA. Expression of miR-143 in the mesenteric fat was significantly up-regulated (3.3-fold, p<0.05) in HFD mice compared to NC mice. MiR-143 expression levels were positively correlated with body weight (R=0.577, p=0.0011) and the mesenteric fat weight (R=0.608, p=0.0005). We also measured expression levels in the mesenteric fat of PPARγ and AP2, whose expression are deeply involved in the development of obesity, insulin resistant and arteriosclerosis. The expression levels of miR-143 were closely correlated with those of PPARγ (R=0.600, p=0.0040) and AP2 (R=0.630, p=0.0022). These findings provide the first evidence for up-regulated expression of miR-143 in the mesenteric fat of HFD-induced obese mice, which might contribute to regulated expression of genes involved in the pathophysiology of obesity.

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Rice Bran Protein Hydrolysates Improve Insulin Resistance and Decrease Pro-inflammatory Cytokine Gene Expression in Rats Fed a High Carbohydrate-High Fat Diet

Nutrients ◽

10.3390/nu7085292 ◽

2015 ◽

Vol 7 (8) ◽

pp. 6313-6329 ◽

Cited By ~ 38

Author(s):

Kampeebhorn Boonloh ◽

Veerapol Kukongviriyapan ◽

Bunkerd Kongyingyoes ◽

Upa Kukongviriyapan ◽

Supawan Thawornchinsombut ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Rice Bran ◽

High Fat Diet ◽

Inflammatory Cytokine ◽

Cytokine Gene Expression ◽

Cytokine Gene ◽

High Fat ◽

High Carbohydrate ◽

Improve Insulin Resistance

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Combined effect of canagliflozin and exercise training on high-fat diet-fed mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00401.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. E492-E503

Author(s):

Kenichi Tanaka ◽

Hirokazu Takahashi ◽

Sayaka Katagiri ◽

Kazuyo Sasaki ◽

Yujin Ohsugi ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Exercise Training ◽

Fatty Liver ◽

High Fat Diet ◽

Characteristic Change ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Sodium Glucose Cotransporter

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been reported to improve obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD) in addition to exercise training, whereas the combined effects remain to be elucidated fully. We investigated the effect of the combination of the SGLT2i canagliflozin (CAN) and exercise training in high-fat diet-induced obese mice. High-fat diet-fed mice were housed in normal cages (sedentary; Sed) or wheel cages (WCR) with or without CAN (0.03% of diet) for 4 wk. The effects on obesity, glucose metabolism, and hepatic steatosis were evaluated in four groups (Control/Sed, Control/WCR, CAN/Sed, and CAN/WCR). Numerically additive improvements were found in body weight, body fat mass, blood glucose, glucose intolerance, insulin resistance, and the fatty liver of the CAN/WCR group, whereas CAN increased food intake and reduced running distance. Exercise training alone, CAN alone, or both did not change the weight of skeletal muscle, but microarray analysis showed that each resulted in a characteristic change of gene expression in gastrocnemius muscle. In particular, in the CAN/WCR group, there was acceleration of the angiogenesis pathway and suppression of the adipogenesis pathway compared with the CAN/Sed group. In conclusion, the combination of an SGLT2i and exercise training improves obesity, insulin resistance, and NAFLD in an additive manner. Changes of gene expression in skeletal muscle may contribute, at least in part, to the improvement of obesity and insulin sensitivity.

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Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00500.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. E31-E41 ◽

Cited By ~ 90

Author(s):

Robert C. Noland ◽

John P. Thyfault ◽

Sarah T. Henes ◽

Brian R. Whitfield ◽

Tracey L. Woodlief ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Weight Gain ◽

High Fat Diet ◽

Oxidative Capacity ◽

Male Rats ◽

High Fat ◽

Endurance Running ◽

Muscle Oxidative Capacity ◽

Obesity And Diabetes

Elevated oxidative capacity, such as occurs via endurance exercise training, is believed to protect against the development of obesity and diabetes. Rats bred both for low (LCR)- and high (HCR)-capacity endurance running provide a genetic model with inherent differences in aerobic capacity that allows for the testing of this supposition without the confounding effects of a training stimulus. The purpose of this investigation was to determine the effects of a high-fat diet (HFD) on weight gain patterns, insulin sensitivity, and fatty acid oxidative capacity in LCR and HCR male rats in the untrained state. Results indicate chow-fed LCR rats were heavier, hypertriglyceridemic, less insulin sensitive, and had lower skeletal muscle oxidative capacity compared with HCR rats. Upon exposure to an HFD, LCR rats gained more weight and fat mass, and their insulin resistant condition was exacerbated, despite consuming similar amounts of metabolizable energy as chow-fed controls. These metabolic variables remained unaltered in HCR rats. The HFD increased skeletal muscle oxidative capacity similarly in both strains, whereas hepatic oxidative capacity was diminished only in LCR rats. These results suggest that LCR rats are predisposed to obesity and that expansion of skeletal muscle oxidative capacity does not prevent excess weight gain or the exacerbation of insulin resistance on an HFD. Elevated basal skeletal muscle oxidative capacity and the ability to preserve liver oxidative capacity may protect HCR rats from HFD-induced obesity and insulin resistance.

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Peripancreatic adipose tissue protects against high-fat-diet-induced hepatic steatosis and insulin resistance in mice

International Journal of Obesity ◽

10.1038/s41366-020-00657-6 ◽

2020 ◽

Vol 44 (11) ◽

pp. 2323-2334

Author(s):

Belén Chanclón ◽

Yanling Wu ◽

Milica Vujičić ◽

Marco Bauzá-Thorbrügge ◽

Elin Banke ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Insulin Levels ◽

Fat Depots ◽

Fat Depot

Abstract Background/objectives Visceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice. Subjects/methods Four adipose tissue depots (inguinal, mesenteric, gonadal, and peripancreatic adipose tissue) from chow- and HFD-fed male mice were compared with respect to adipocyte size (n = 4–5/group), cellular composition (FACS analysis, n = 5–6/group), lipogenesis and lipolysis (n = 3/group), and gene expression (n = 6–10/group). Radioactive tracers were used to compare lipid and glucose metabolism between these four fat depots in vivo (n = 5–11/group). To determine the role of PAT in obesity-associated metabolic disturbances, PAT was surgically removed prior to challenging the mice with HFD. PAT-ectomized mice were compared to sham controls with respect to glucose tolerance, basal and glucose-stimulated insulin levels, hepatic and pancreatic steatosis, and gene expression (n = 8–10/group). Results We found that PAT is a tiny fat depot (~0.2% of the total fat mass) containing relatively small adipocytes and many “non-adipocytes” such as leukocytes and fibroblasts. PAT was distinguished from the other fat depots by increased glucose uptake and increased fatty acid oxidation in both lean and obese mice. Moreover, PAT was the only fat depot where the tissue weight correlated positively with liver weight in obese mice (R = 0.65; p = 0.009). Surgical removal of PAT followed by 16-week HFD feeding was associated with aggravated hepatic steatosis (p = 0.008) and higher basal (p < 0.05) and glucose-stimulated insulin levels (p < 0.01). PAT removal also led to enlarged pancreatic islets and increased pancreatic expression of markers of glucose-stimulated insulin secretion and islet development (p < 0.05). Conclusions PAT is a small metabolically highly active fat depot that plays a previously unrecognized role in the pathogenesis of hepatic steatosis and insulin resistance in advanced obesity.

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Adult mice maintained on a high-fat diet exhibit object location memory deficits and reduced hippocampal SIRT1 gene expression

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2012.04.005 ◽

2012 ◽

Vol 98 (1) ◽

pp. 25-32 ◽

Cited By ~ 98

Author(s):

Frankie D. Heyward ◽

R. Grace Walton ◽

Matthew S. Carle ◽

Mark A. Coleman ◽

W. Timothy Garvey ◽

...

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Memory Deficits ◽

Object Location ◽

High Fat ◽

Location Memory ◽

Adult Mice ◽

Object Location Memory ◽

Sirt1 Gene

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Kappa-Carrageenan Inhibited the High-Fat-Diet-Induced Obesity Through Up-Regulating the Hepatic Sirt1 Gene Expression

Current Developments in Nutrition ◽

10.1093/cdn/nzab041_018 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 503-503

Author(s):

Zhiji Huang ◽

Yafang Ma ◽

Chunbao Li

Keyword(s):

Gene Expression ◽

Weight Gain ◽

Energy Expenditure ◽

Energy Intake ◽

High Fat Diet ◽

The Body ◽

High Fat ◽

Diet Induced Obesity ◽

Sirt1 Gene ◽

Kappa Carrageenan

Abstract Objectives Kappa-Carrageenan(CGN) is a widely used food additive in the meat industry and a highly viscous soluble dietary fiber which can hardly be fermented. It has been shown to be able to regulate the energy metabolism and inhibit diet-induced obesity. However, the mechanism is not well understood. The purpose of this study is to investigate the mechanisms of κ-carrageenan to inhibit the body weight gain. Methods A high-fat diet incorporated with lard, pork protein and CGN (2% or 4%, w/w) was given to C57BL/6J mice for 90 days. The energy intake and weight changes were measured every three days. After the dietary intervention, mice were sacrificed, liver and epididymal adipose tissues were taken for real-time polymerase chain reaction (RT-qPCR) analysis. Results The CGN in the high-fat diet restricted weight gain by decreasing liver and adipose mass without inhibiting energy intake. The genes involving energy expenditure such as Acox1, Acadl, CPT-1A and Sirt1 were upregulated in the mice fed with carrageenan. However, the genes responsible for lipid synthesis were not significantly different compared to the diet-induced obese model. Conclusions The anti-obesity effect of the CGN in high-fat diet could be highly related to the enhancement of energy expenditure through up-regulating the downstream genes which promote β-oxidation by increasing the Sirt1 gene expression in liver. Funding Sources Ministry of Science and Technology of the People's Republic of China (10000 Talent Project)

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High Fiber and Beta Carotene from Sweet Potatoes and Pumpkin Improve Insulin Resistance by Inhibition of Sterol Regulatory Binding Protein 1c in Liver of Hypertriglyceridemic Rats

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.5354 ◽

2020 ◽

Vol 8 (A) ◽

pp. 898-903

Author(s):

Sunarti Sunarti ◽

Umar Santoso ◽

Abrory Agus Cahya Pramana ◽

Emy Huriyati ◽

Dianandha Septiana Rubi

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Binding Protein ◽

Beta Carotene ◽

Male Rats ◽

Standard Diet ◽

Model Assessment ◽

High Fat ◽

High Fiber ◽

Improve Insulin Resistance

BACKGROUND: High sterol regulatory binding protein 1c (SREBP-1c) gene expression increases triglyceride synthesis, which induces insulin resistance. Short-chain fatty acids (SCFAs) from fiber fermentation and beta carotene may inhibit SREBP-1c gene expression. AIM: The aim of this study was to evaluate the high fiber and beta carotene diet on improving insulin resistance in hypertriglyceridemia rats. METHODS: A total of 25 Wistar male rats were divided into five groups: (1) Normal control (NC); (2) hypertriglyceridemia control (HC); (3) hypertriglyceridemia rats with treatment 1 (HT1); (4) hypertriglyceridemia rats with treatment 2 (HT2); and (5) hypertriglyceridemia rats with treatment 1 (HT3). The HT1, HT2, and HT3 received fiber 1.0 g; 2.0 g; and 3.1 g and beta carotene 725.7 μg; 1451.5 μg; and 2177.2 μg per day, respectively, for 6 weeks. The HC received high fat and fructose diet and the NC received a standard diet. The levels of triglyceride were analyzed using the colorimetric method before and after treatment. At the end of the study, the expression of SREBP-1c was identified by a quantitative polymerase chain reaction. RESULTS: High fat and fructose diet increased the levels of triglyceride (36.53 ± 1.27 vs. 119.79 ± 7.73), but high fiber and beta carotene diet can reduce triglyceride levels in HT1 (94.58 ± 4.53 vs. 77.70 ± 7.97); HT2 (115.58 ± 4.76 vs. 66.90 ± 3.11); and HT3 (103.87 ± 7.47 vs. 62.06 ± 4.45). The decreased triglyceride levels were related to low SREBP-1c gene expression, especially in the liver. Low SREBP-1c gene expression was correlated with homeostatic model assessment of insulin resistance index with r = 0.414; p < 0.05 in the liver and r = 0.158; p > 0.05 in white adipose tissues. CONCLUSION: High fiber and beta carotene diet can improve insulin resistance through inhibition of SREBP-1c gene expression.

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Pineapple Juice Ameliorates the High Fat Diet-induced Alterations in Cardiac Gene Expression Pattern in Male Rats

International Journal of Biochemistry Research & Review ◽

10.9734/ijbcrr/2016/32056 ◽

2016 ◽

Vol 15 (4) ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Mohamed Ahmed

Keyword(s):

Gene Expression ◽

Expression Pattern ◽

High Fat Diet ◽

Gene Expression Pattern ◽

Male Rats ◽

High Fat ◽

Pineapple Juice ◽

Cardiac Gene Expression ◽

Cardiac Gene

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Effects of Diet-Induced Obesity on Hypothalamic Kisspeptin-Neurokinin-Dynorphin (KNDy) Neurons and Luteinizing Hormone Secretion in Sex Hormone-Primed Male and Female Rats

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1094 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A537-A537

Author(s):

Shiori Minabe ◽

Kinuyo Iwata ◽

Hitoshi Ozawa

Keyword(s):

Gene Expression ◽

Luteinizing Hormone ◽

High Fat Diet ◽

Female Rats ◽

Male Rats ◽

High Fat ◽

Neurokinin B ◽

Male And Female ◽

Male And Female Rats ◽

Kndy Neurons

Abstract Metabolic stress resulting from a nutrient excess causes infertility in both sexes. Kisspeptin-neurokinin B-dynorphin (KNDy) neurons in the arcuate nucleus (ARC) have been suggested to be key players in reproduction via direct stimulation of gonadotropin-releasing hormone (GnRH) and subsequent gonadotropin release in mammalian species. In this study, we investigated the sex differences in the effects of a high-fat diet (HFD) on KNDy-associated gene expression in the ARC to determine the pathogenic mechanism underlying obesity-induced infertility. Wistar-Imamichi strain male and female rats (7 weeks of age) were fed either a standard diet (10% calories from fat) or high-fat diet (45% calories from fat) for 4 months. In male rats, the HFD caused a significant suppression of Kiss1(encoding kisspeptin), Tac3(encoding neurokinin B), and Pdyn(encoding dynorphin A) gene expression in the ARC, resulting in a decrease in plasma luteinizing hormone (LH) levels. In female rats, 58% of the HFD-fed female rats exhibited irregular estrous cycles, while the other rats showed regular cycles. LH pulses were found, and the numbers of ARC Kiss1-,Tac3-, and Pdyn-expressing cells were high in control animals and almost allHFD-fed female rats, but two out of 10 rats showed profound HFD-induced suppression of LH pulse frequency and reduction in these cells. No statistical differences in LH secretion or ARC KNDy gene expression were observed between HFD-fed and control female rats. Additionally, the number of Gnrh1-expressing cells in the preoptic area was comparable between the groups in both sexes. Our findings revealed that HFD-fed male rats showed KNDy-dependent infertility, while irregular menstruation was mainly induced by KNDy-independent pathways during the incipient stage of obese infertility in female rats. Taken together, hypothalamic kisspeptin neurons in male rats may be susceptible to HFD-induced obesity compared with those in female rats.

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