scholarly journals Renal (Pro)renin Receptor Contributes to High Fat Diet-Induced Obesity

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A55-A55
Author(s):  
Silas Allen Culver ◽  
Helmy M Siragy

Abstract Recently we reported that (Pro)renin receptor (PRR) expression increases in the renal nephron during high fat diet intake. This study evaluated the role of renal PRR in the development of obesity. Eight-week old male mice with inducible nephron specific PRR knockout (KO) and wild type littermate (control) were fed either normal diet (ND, 12%kcal fat) or high fat diet (HFD, 45%kcal fat) for 6 months. KO Mice underwent induction of PRR KO with oral doxycycline 2mg/mL in 2% sucrose water for 12 days prior to starting diet. Compared to ND, HFD increased body weight by 40% (p<0.05) in control mice. In contrast, compared to control mice fed HFD, body weight of induced PRR KO on HFD was reduced by 56% (p<0.05). Total body fat increased by 179% (p<0.05) with HFD compared to ND control mice while it did not increase in PRR KO mice fed HFD. Twenty-four-hour caloric intake was not reduced in KO mice compared to controls while there were significant increases in nocturnal VO2 by 31% and respiratory exchange by 10% (p<0.05) in HFD PRR KO mice compared to HFD fed controls. Unexpectedly, urine glucose excretion significantly increased in PRR KO mice on both ND and HFD. Our results demonstrate that nephron specific PRR KO reduced diet induced obesity and adiposity, while increasing energy expenditure. Future investigations are warranted to elucidate the mechanisms by which renal PRR contributes to the development of obesity.

Endocrinology ◽  
2021 ◽  
Author(s):  
Silas A Culver ◽  
Safia Akhtar ◽  
Callie Rountree-Jablin ◽  
Susanna R Keller ◽  
Helen P Cathro ◽  
...  

Abstract ATP6AP2 expression is increased in the nephron during high fat diet (HFD) and its knockout (ATP6AP2 KO) reduces body weight (WT) in mice. We evaluated the contribution of ATP6AP2 to urinary glucose (UG) and albumin (Ualb) handling during HFD. We hypothesized that nephron ATP6AP2 KO increases UG and Ualb and minimizes HFD-induced obesity. Eight-week old male C57BL/6J mice with inducible nephron specific ATP6AP2 KO and non-induced controls (C) were fed either normal diet (ND, 12% kcal fat) or HFD (45% kcal fat) for 6 months. ATP6AP2 KO mice on ND had 20% (p<0.01) lower WT compared to C. HFD fed mice had 41% (p<0.05) greater WT than ND fed C. In contrast, ATP6AP2 KO abrogated the increase in WT induced by HFD by 40% (p<0.05). Mice on HFD had less caloric intake compared to ND controls (p<0.01). There were no significant differences in metabolic rate between all groups. UG and Ualb was significantly increased in ATP6AP2 KO mice on both ND and HFD. ATP6AP2 KO showed greater levels of proximal tubule apoptosis and histologic evidence of proximal tubule injury. In conclusion, our results demonstrate that nephron specific ATP6AP2 KO is associated with glucosuria and albuminuria, most likely secondary to renal proximal tubule injury and/or dysfunction. Urinary loss of nutrients may have contributed to the reduced WT of knockout mice on ND and lack of WT gain in response to HFD. Future investigation should elucidate the mechanisms by which loss of renal ATP6AP2 causes proximal tubule injury and dysfunction.


Author(s):  
Sarita Mulkalwar ◽  
Tanya Gupta ◽  
Vishwanath Kulkarni ◽  
A. V. Tilak ◽  
B. T. Rane ◽  
...  

Background: As of 2018, 2.1 billion people nearly 30% of the world’s population are either obese or overweight. Worldwide obesity has nearly tripled since 1975. It is an emerging health problem with major adverse effects on health. It is a risk factor for many chronic diseases but is best known for its role in metabolic syndrome, which can lead to type 2 diabetes mellitus as well as cardiovascular diseases. Anti-obesity drugs are available but have many side effects. Voglibose, an antidiabetic drug, is an alpha glucosidase inhibitor which shows promising results in the reduction of body weight with minimal side effects.Methods: Voglibose (7 mg/kg) was administered to rats fed with normal laboratory chows and high fat diet to see its effect on body weight, body mass index, abdominal and thoracic circumference, and lipid profile at the end of 12 weeks.Results: Administration of voglibose significantly reduced food consumption, feed efficiency and increase in body weight induced by high fat diet in rats. Rats fed on normal diet also showed reductions in the same parameters, suggesting its weight lowering effect. Reductions in the anthropometric measurements, hypolipidemic effects and glucose lowering effects were also observed.Conclusions: Voglibose prevented high fat diet-induced obesity and improvement in metabolic profile, which ultimately has systemic effects on body weight in rats. Further studies are needed to see its potential therapeutic use in obese patients with type 2 diabetes mellitus, and related complications.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Feten Zar Kalai ◽  
Junkyu Han ◽  
Riadh Ksouri ◽  
Abdelfatteh El Omri ◽  
Chedly Abdelly ◽  
...  

Nitraria retusais an edible halophyte, used in Tunisia for several traditional medicine purposes. The present study investigated the antiobesity effects ofNitraria retusaethanol extract (NRE) in 3T3-L1 cells using different doses and in high-fat diet-induced obesity in mice. Male C57B6J/L mice were separately fed a normal diet (ND) or a high-fat diet (HFD) and daily administrated with NRE (50, 100 mg/kg) or one for 2 days with Naringenin (10 mg/kg). NRE administration significantly decreased body weight gain, fat pad weight, serum glucose, and lipid levels in HFD-induced obese mice. To elucidate the mechanism of action of NRE, the expression of genes involved in lipid and carbohydrate metabolism were measured in liver. Results showed that mice treated with NRE demonstrated a significant decrease in cumulative body weight and fat pad weight, a significant lowering in glucose and triglycerides serum levels, and an increase in the HDL-cholesterol serum level. Moreover mRNA expression results showed an enhancement of the expression of genes related to liver metabolism. Our findings suggest that NRE treatment had a protective or controlling effect against a high fat diet-induced obesity in C57B6J/L mice through the regulation of expression of genes involved in lipolysis and lipogenesis and thus the enhancement of the lipid metabolism in liver.


2019 ◽  
Author(s):  
Lisa Y. Beppu ◽  
Xiaoyao Qu ◽  
Giovanni J. Marrero ◽  
Allen N. Fooks ◽  
Adolfo B. Frias ◽  
...  

ABSTRACTCrosstalk between the immune system and adipocytes is critical for maintaining tissue homeostasis and regulating chronic systemic inflammation during diet-induced obesity (DIO). How visceral adipose tissue resident regulatory T cells (aTregs) signal to adipocytes in the visceral adipose tissue (VAT) is not understood. Here we show that Treg-specific ablation of the transcriptional regulator Blimp-1 resulted in increased insulin sensitivity, decreased body weight and increased Ucp-1 in adipocytes in high fat diet (HFD)-fed mice. Mechanistically, we demonstrate that Blimp-1 drives IL-10 production in Tregs, thus suppressing beiging and energy expenditure in adipocytes. Moreover, IL-10 mRNA expression positively correlated with increasing body weight in humans. These findings reveal a surprising relationship between aTregs and adipocytes in promoting insulin resistance during excessive caloric intake, placing Blimp-1-regulated IL-10 expression by aTregs at a critical juncture in the development of obesity and its associated comorbidities in mice and humans.SUMMARYHere we show that ablation of Blimp-1 in adipose tissue resident Tregs (aTregs) leads to decreased IL-10 production, resulting in increased Ucp-1 expression and beiging by adipocytes and protection from diet-induced obesity and insulin resistance.


Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1914
Author(s):  
Na-Yeon Kim ◽  
Shalom Sara Thomas ◽  
Dae-Il Hwang ◽  
Ji-Hye Lee ◽  
Kyung-Ah Kim ◽  
...  

The present study investigated the synergic effect of extracts of Morus alba (MA) and Aronia melanocarpa (Michx.) (AR) against high-fat diet induced obesity. Four-week-old male C57BL/6J mice were randomly divided into five groups that were fed for 14 weeks with a normal diet (ND), high-fat diet (HD), HD with M. alba 400 mg/kg body weight (MA), HD with A. melanocarpa 400 mg/kg body weight (AR), or HD with a mixture (1:1, v/v) of M. alba and A. melanocarpa (400 mg/kg) (MA + AR). Treatment with MA, AR, and MA + AR for 14 weeks reduced high fat diet-induced weight gain and improved serum lipid levels, and histological analysis revealed that MA and AR treatment markedly decreased lipid accumulation in the liver and adipocyte size in epididymal fat. Furthermore, micro-CT images showed MA + AR significantly reduced abdominal fat volume. Expression levels of genes involved in lipid anabolism, such as SREBP-1c, PPAR-γ, CEBPα, FAS, and CD36 were decreased by MA + AR treatment whereas PPAR-α, ACOX1, and CPT-1a levels were increased by MA + AR treatment. Protein expression of p-AMPK and p-ACC were increased in the MA + AR group, indicating that MA + AR ameliorated obesity by upregulating AMPK signaling. Together, our findings indicate that MA and AR exert a synergistic effect against diet-induced obesity and are promising agents for managing obesity.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Souravh Bais ◽  
Guru Sewak Singh ◽  
Ramica Sharma

In the present study, the methanolic extract of Moringa oleifera leaves (MEMOL) was evaluated for antiobesity activity in rats. The antiobesity potential of MEMOL was studied against high fat diet-induced obesity (HFD) in rats. In this study, chronic administration of HFD in rats produced hypercholesterolemia (116.2 ± 0.27 mg/dL), which led to an increase in the body weight (225 gr), total cholesterol, triglycerides (263.0 ± 4.69 mg/dL), and attenuation in the levels of HDL (34.51 ± 2.20 mg/dL) as well as changes in body temperature of animals. Treatment of obese rats with MEMOL for 49 days resulted in a significant (P<0.001) change in body weight, total cholesterol, triglycerides, and LDL level along with a significant (P<0.001) increase in body temperature as compared to the HFD-induced obesity. MEMOL treated rats also showed a significant decrease in the level of liver biomarkers, organ weight, and blood glucose level. Further, rats treated with MEMOL (200 mg and 400 mg/kg) show reduced atherogenic index (1.7 ± 0.6 and 0.87 ± 0.76). The results indicate that the rats treated with Moringa oleifera (MO) have significantly attenuated the body weight without any change in the feed intake and also elicited significant thermogenic effect and to act as hypolipidemic and thermogenic property in obesity related disorders.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Matthew R Peterson ◽  
Samantha Haller ◽  
Tracy Ta ◽  
Luiza Bosch ◽  
Aspen Smith ◽  
...  

NLR family, pyrin domain-containing 3 (NLRP3) is a pattern recognition receptor responsible for perpetuating an inflammatory response through production of pro-inflammatory cytokines IL-1β and IL-18. It has been implicated in the sustained inflammatory response in obesity and multiple cardiovascular disease conditions. In order to investigate NLRP3 as a potential therapeutic target in metabolic syndrome, C57BL/6 wild-type (WT) and NLRP3 knockout (NLRP3-\-) mice were fed a normal diet (ND; 12% fat chow) or a high fat diet (HFD; 45% fat chow) for 5 months. At 5 months, echocardiography and glucose tolerance tests (GTTs) were performed. Cardiac function assessed by fractional shortening (FS) was significantly impaired by HFD feeding in the WT group (0.335 HFD vs. 0.456 ND; p<0.05) but not in the NLRP3-\- (0.449 HFD vs. 0.492 ND; p>0.05). FS was higher in NLRP3-\-HFD than in WT-HFD (p<0.05). Two-dimensional analysis shows the FS difference between NLRP3-\-HFD and WT-HFD was primarily explained by the difference in left ventricular end-systolic dimension (0.2716 cm WT vs. 0.1883 cm NLRP3-\-; p<0.05). Glucose tolerance measured by area under the curve (AUC) was significantly impaired by HFD feeding for both WT (23183 ND vs. 57298 HFD; p<0.001) and NLRP3-\- (23197 ND vs. 44626 HFD; p<0.001), but significantly better in the NLRP3-\-HFD than in WT-HFD (p<0.01). HFD feeding increased fasting blood glucose (FBG) for both WT (97.7 mg . dl -1 ND vs. 164.7 mg . dl -1 HFD; p<0.01) and NLRP3-\- (80.50 mg . dl -1 ND vs. 108.8 mg . dl -1 HFD; p<0.05), but significantly less in NLRP3-\- mice (NLRP3-\- vs. WT; p<0.05). For GTTs, body weight was significantly higher in the WT than NLRP3-\- fed HFD (47.93 g vs. 36.5 g; p<0.001). Body weight explained 92% of variation in glucose tolerance (p<0.0001) and 69% of variation in fasting blood glucose (p<0.0001). WT-HFD averaged 1.31X heavier than NLRP3-\-HFD, while the AUC for the IGTT was 1.28X larger for the WT-HFD than NLRP3-\-HFD. Body weights were not significantly different between genotypes at the time of echo. The results suggest that knockout of NLRP3 may be protective against HFD induced cardiovascular dysfunction. A protective effect on glucose tolerance is not strongly supported.


2017 ◽  
Vol 49 (10) ◽  
pp. 793-800 ◽  
Author(s):  
Guoqiang Fan ◽  
Yu Qiao ◽  
Shixing Gao ◽  
Jun Guo ◽  
Ruqian Zhao ◽  
...  

AbstractZinc alpha2 glycoprotein (ZAG) is a new type of adipokine involved in adipose tissue mobilization, however, little is known about its lipid metabolism effect in liver. Therefore, we investigated the effects of ZAG in the regulation of hepatic lipid accumulation. Mice were randomly divided into two groups; one was fed a normal diet and another was fed a high-fat diet for eight weeks to establish obesity model. After that, the normal diet group was divided into ND (injection of pcDNA3.1) and NDZ (injection of ZAG recombinant plasmid) and the high-fat diet group was divided into HF (injection of pcDNA3.1) and HFZ (injection of ZAG recombinant plasmid). The mice were weighed once per week and injected with plasmid once every three days for eight times. The results showed that body weight and hepatic TG content were decreased dramatically in HFZ group compared with HF group. The stearoyl-CoAdesaturase1 (SCD1) and Acyl-CoA Synthetase-1 (ACSS1) protein levels in HFZ group were significantly decreased. Furthermore, phosphorylated hormone sensitive lipase (P-HSL) was significantly higher in HFZ group. In HFZ group, hepatic fatty acid translocase (CD36) and fatty acids binding protein-1 (FABP1) protein levels were reduced. In addition, the expression of phosphorylated protein kinase A (PPKA) in HFZ group was higher than the HF group. Meanwhile, NDZ group showed significantly decreased body weight and increased P-HSL level though the hepatic TG content showed no significantly changes compared with the ND group. Therefore, we conclude that ZAG may be beneficial for preventing high-fat-diet-induced hepatic lipid metabolic disorders.


2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Zhen Wang ◽  
Lance T. Jaynes ◽  
Sydney P. Moak ◽  
Xuemei Dai ◽  
Yiling Fu ◽  
...  

1986 ◽  
Vol 56 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Stephen Rattigan ◽  
Peter R.C. Howe ◽  
Michael G. Clark

1. Energy intakes, body-weights, body fat index, total body fat and interscapular brown adipose tissue (IBAT) were examined in adult male, spontaneously hypertensive, stroke-prone (SHR-SP) rats and normotensive Wistar/Kyoto (WKY) controls given one of four diets for 33 d: (a) a starch diet, (b) a starch diet and a sucrose solution drinking option, (c) an 80xenergy from fat (F80) diet, (d) the F80 diet and a sucrose drinking option.2. The SHR-SP rats showed a complete resistance to obesity on all four diets. For the high-fat diet the WKY animals became markedly obese with approximately two-fold increases in body-weight gain and body fat index when compared with the SHR-SP rats. The gain in total body fat was also significantly greater. IBAT as a percentage of total body-weight did not differ between the WKY and SHR-SP groups.3. Compared with the WKY animals, the SHR-SP rats showed a reduced food intake but had the same potential to gain weight from the high-fat diet.4. It is concluded that the resistance to obesity by the hypertensive animals is the result of a diminished energy intake.


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