Glycolipid Metabolism Disorder in the Liver of Obese Mice Is Improved by TUDCA via the Restoration of Defective Hepatic Autophagy

Objective.Tauroursodeoxycholic acid (TUDCA) has been considered an important regulator of energy metabolism in obesity. However, the mechanism underlying how TUDCA is involved in insulin resistance is not fully understood. We tested the effects of TUDCA on autophagic dysfunction in obese mice.Material and Methods.500 mg/kg of TUDCA was injected into obese mice, and metabolic parameters, autophagy markers, and insulin signaling molecular were assessed by Western blotting and real-time PCR.Results.The TUDCA injections in the obese mice resulted in a reduced body weight gain, lower blood glucose, and improved insulin sensitivity compared with obese mice that were injected with vehicle. Meanwhile, TUDCA treatment not only reversed autophagic dysfunction and endoplasmic reticulum stress, but also improved the impaired insulin signaling in the liver of obese mice. Additionally, the same results obtained with TUDCA were evident in obese mice treated with the adenoviral Atg7.Conclusions.We found that TUDCA reversed abnormal autophagy, reduced ER stress, and restored insulin sensitivity in the liver of obese mice and that glycolipid metabolism disorder was also improved via the restoration of defective hepatic autophagy.

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Beneficial effects of a combination of Clostridium cochlearium and Lactobacillus acidophilus on body weight gain, insulin sensitivity and gut microbiota in high-fat diet induced obese mice

Nutrition ◽

10.1016/j.nut.2021.111439 ◽

2021 ◽

pp. 111439

Author(s):

Fei Yang ◽

Wen-Jun Zhu ◽

Paba Edirisuriya ◽

Qing Ai ◽

Kai Nie ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Insulin Sensitivity ◽

Lactobacillus Acidophilus ◽

High Fat Diet ◽

Body Weight Gain ◽

Obese Mice ◽

High Fat ◽

Beneficial Effects ◽

Clostridium Cochlearium

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Peer Review #1 of "Rice koji reduced body weight gain, fat accumulation, and blood glucose level in high-fat diet-induced obese mice (v0.1)"

10.7287/peerj.540v0.1/reviews/1 ◽

2014 ◽

Keyword(s):

Body Weight ◽

Weight Gain ◽

Blood Glucose ◽

Blood Glucose Level ◽

Glucose Level ◽

High Fat Diet ◽

Body Weight Gain ◽

Obese Mice ◽

High Fat ◽

Reduced Body

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Fibroblast growth factor 21 reverses suppression of adiponectin expression via inhibiting endoplasmic reticulum stress in adipose tissue of obese mice

Experimental Biology and Medicine ◽

10.1177/1535370216677354 ◽

2016 ◽

Vol 242 (4) ◽

pp. 441-447 ◽

Cited By ~ 8

Author(s):

Qinyue Guo ◽

Lin Xu ◽

Jiali Liu ◽

Huixia Li ◽

Hongzhi Sun ◽

...

Keyword(s):

Insulin Resistance ◽

Endoplasmic Reticulum ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Growth Factor ◽

Er Stress ◽

Insulin Signaling ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Obese Mice

Fibroblast growth factor 21 (FGF21) has recently emerged as a novel endocrine hormone involved in the regulation of glucose and lipid metabolism. However, the exact mechanisms whereby FGF21 mediates insulin sensitivity remain not fully understood. In the present study, FGF21was administrated in high-fat diet-induced obese mice and tunicamycin-induced 3T3-L1 adipocytes, and metabolic parameters, endoplasmic reticulum (ER) stress indicators, and insulin signaling molecular were assessed by Western blotting. The administration of FGF21 in obese mice reduced body weight, blood glucose and serum insulin, and increased insulin sensitivity, resulting in alleviation of insulin resistance. Meanwhile, FGF21 treatment reversed suppression of adiponectin expression and restored insulin signaling via inhibiting ER stress in adipose tissue of obese mice. Additionally, suppression of ER stress via the ER stress inhibitor tauroursodeoxycholic acid increased adiponectin expression and improved insulin resistance in obese mice and in tunicamycin-induced adipocytes. In conclusion, our results showed that the administration of FGF21 reversed suppression of adiponectin expression and restored insulin signaling via inhibiting ER stress under the condition of insulin resistance, demonstrating the causative role of ER stress in downregulating adiponectin levels.

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Adipose tissue transplantation protects ob/ob mice from obesity, normalizes insulin sensitivity and restores fertility

Journal of Endocrinology ◽

10.1677/joe.1.06150 ◽

2005 ◽

Vol 186 (1) ◽

pp. 203-211 ◽

Cited By ~ 48

Author(s):

Simon Klebanov ◽

Clinton M Astle ◽

Olga DeSimone ◽

Vitaly Ablamunits ◽

David E Harrison

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Insulin Sensitivity ◽

Therapeutic Potential ◽

Body Weight Gain ◽

Hormone Replacement ◽

Tolerance Test ◽

Reduced Body ◽

Insulin Tolerance

Adipose tissue affects metabolism by secreting various adipokines. Lipodystropic mice benefit both from leptin replacement therapy and from transplantation of normal fat. Leptin-deficient Lepob/Lepob (ob/ob) mice can also be treated with leptin. Surprisingly, there have been no reports of successful treatment of obese ob/ob mice by transplantation of normal white adipose tissue (WAT). If WAT transplantation is ineffective in treating insulin resistance and diabetes in obese individuals, its applicability may be limited in humans as such abnormalities are usually associated with obesity. In the current study, we tested whether WAT transplantation might prevent, and even reverse, abnormalities characteristic of ob/ob mice. To assess the preventive potential, 6-week-old ob/ob mice were transplanted, subcutaneously, with gonadal fat pads from normal mice. Profound effects on multiple physiological phenotypes were achieved despite leptin levels below 25% of those in control mice. WAT from one donor reduced body weight gain, and WAT from 4 or 8 donors prevented obesity in ob/ob mice. Nonfasting insulin levels and insulin tolerance test were normalized. Corticosterone elevation was also prevented. Finally, WAT from 4 donors restored fertility in ob/ob females. The effects of WAT transplantation were long-lasting, with body weight gain suppressed for at least 40 weeks. To assess the therapeutic potential, obese 13-month-old ob/ob mice with a long history of leptin deficiency were used. Their body weight decreased by approximately 50% when transplanted with WAT from 8 donors. As in young recipients, transplantation greatly reduced nonfasting insulin, suggesting normalized insulin sensitivity. Thus, WAT transplantation was effective for both prevention and therapy. In the future, WAT transplantation may become a useful alternative to hormone replacement in treating not only lipodystropy, but also certain types of obesity.

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Lactiplantibacillusplantarum ATG-K2 Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese Mice by Modulating the Gut Microbiome

International Journal of Molecular Sciences ◽

10.3390/ijms222312665 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12665

Author(s):

Young-Sil Lee ◽

Eun-Jung Park ◽

Gun-Seok Park ◽

Seung-Hyun Ko ◽

Juyi Park ◽

...

Keyword(s):

Gut Microbiome ◽

Lipid Accumulation ◽

High Fat Diet ◽

Body Weight Gain ◽

Obese Mice ◽

High Fat ◽

Major Health Problem ◽

Beneficial Effects ◽

Reduced Body ◽

Tnf Α

Obesity is a major health problem. Compelling evidence supports the beneficial effects of probiotics on obesity. However, the anti-obesity effect of probiotics remains unknown. In this study, we investigated the anti-obesity effects and potential mechanisms of Lactiplantibacillus plantarum ATG-K2 using 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. 3T3-L1 cells were incubated to determine the effect of lipid accumulation with lysate of L. plantarum ATG-K2. Mice were fed a normal fat diet or HFD with L. plantarum ATG-K2 and Orlistat for 8 weeks. L. plantarum ATG-K2 inhibited lipid accumulation in 3T3-L1 adipocytes, and reduced body weight gain, WAT weight, and adipocyte size in HFD-induced obese mice, concurrently with the downregulation of PPARγ, SREBP1c, and FAS and upregulation of PPARα, CTP1, UCP1, Prdm16, and ND5. Moreover, L. plantarum ATG-K2 decreased TG, T-CHO, leptin, and TNF-α levels in the serum, with corresponding gene expression levels in the intestine. L. plantarum ATG-K2 modulated the gut microbiome by increasing the abundance of the Lactobacillaceae family, which increased SCFA levels and branched SCFAs in the feces. L. plantarum ATG-K2 exhibited an anti-obesity effect and anti-hyperlipidemic effect in 3T3-L1 adipocytes and HFD-induced obese mice by alleviating the inflammatory response and regulating lipid metabolism, which may be influenced by modulation of the gut microbiome and its metabolites. Therefore, L. plantarum ATG-K2 can be a preventive and therapeutic agent for obesity.

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Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice—a new potential probiotic for appetite and body weight management

International Journal of Obesity ◽

10.1038/s41366-019-0515-9 ◽

2020 ◽

Vol 44 (5) ◽

pp. 1041-1051 ◽

Cited By ~ 11

Author(s):

Romain Legrand ◽

Nicolas Lucas ◽

Manon Dominique ◽

Saida Azhar ◽

Camille Deroissart ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Weight Management ◽

Fat Mass ◽

Body Weight Gain ◽

Overweight And Obesity ◽

Obese Mice ◽

Hafnia Alvei ◽

Reduced Body

Abstract Background/objectives Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity. Methods The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alvei HA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/ob and high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the “MetaHIT” database. Results Chronic per os administration of native but not ClpB-deficient E.coli strain reduced body weight gain (p < 0.05) and daily meal frequency (p < 0.001) in ob/ob mice. Oral gavage of H.alvei for 18 and 46 days in ob/ob and HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p < 0.05) and decreased food intake in hyperphagic ob/ob mice (p < 0.001). Elevated fat tissue levels of phosphorylated hormone-sensitive lipase were detected in H.alvei -treated ob/ob mice (p < 0.01). Enterobacterial ClpB gene richness was lower in obese vs. non-obese humans (p < 0.0001) and correlated negatively with BMI in genera of Enterobacter, Klebsiella and Hafnia. Conclusions H.alvei HA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alvei as a probiotic for appetite and body weight management in overweight and obesity.

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SUN-662 Praliciguat, a Clinical-Stage Soluble Guanylate Cyclase Stimulator, Improves Lipid Handling and Insulin Sensitivity in Diet-Induced Obese Mice

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.917 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Chad D Schwartzkopf ◽

Guang Liu ◽

John R Hadcock ◽

Mark G Currie ◽

Jamie L Masferrer ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

White Adipose Tissue ◽

Insulin Signaling ◽

Soluble Guanylate Cyclase ◽

Clinical Stage ◽

Metabolic Effects ◽

Obese Mice ◽

Pathway Activity ◽

Diet Induced Obesity

Abstract Praliciguat (PRL) is a soluble guanylate cyclase (sGC) stimulator which in animal models distributes broadly to tissues and elicits hemodynamic, anti-inflammatory, anti-fibrotic, and metabolic effects. Here, we assessed metabolic effects of PRL in a mouse diet-induced obesity model. Six-week-old male C57BL/6N mice were maintained on a low-fat diet (LFD, lean mice) or placed on a 60% high-fat diet (HFD, obese mice). At age 14 weeks, one group of obese mice was maintained on HFD (obese controls) and one group of obese mice was switched to HFD formulated with PRL to achieve a Cmax similar to a 6-mg/kg oral dose (PRL-treated mice). After 38 days of treatment, an oral lipid tolerance test (LTT) was conducted. In a 2nd study under the same dosing paradigm, overnight fasted blood and organs were collected on day 28. As reported previously (1), compared to obese controls, PRL-treated mice had lower fasting insulin (-28%), HOMA-IR (-26%) and triglycerides (-16%) as well as lower plasma triglycerides AUC after LTT (-34%). Gene expression and phosphorylated proteins associated with insulin pathways were measured in liver, skeletal muscle and white adipose tissue. PRL treatment normalized expression of genes involved in lipid handling (liver Pnpla3, Slc27a1, Lpl; muscle Lipe; white adipose tissue Fdft1, Ppara). Expression of proinflammatory genes (liver Tnf; muscle Ccl2; white adipose tissue Akt1, Icam1) was lower in PRL-treated mice than in obese controls. Liver insulin signaling was assessed by determining pAKT (T308) and pAKT (S473), markers of PI3K pathway activity and pERK, a marker of MAPK pathway activity. Compared to lean mice, pAKT (T308) and pERK were lower in obese controls, whereas pAKT (S473) was similar; PRL-treated mice had higher pAKT (T308) and pAKT (S473) compared to obese controls while pERK was unchanged. In skeletal muscle and white adipose tissue, levels of pVASP, a key mediator of the sGC pathway, were higher in PRL-treated mice than in obese controls. In summary, PRL improved insulin sensitivity and lipids in diet-induced obese mice by affecting mechanisms of lipid handling, inflammation, and insulin signaling in key tissues associated with metabolism. 1. Author information excluded, 1924-P: Praliciguat, a Clinical-Stage sGC Stimulator, Improves Insulin Sensitivity, Lipid Tolerance, and Energy Utilization in a Mouse Diet-Induced Obesity Model Housed at Thermoneutrality. Diabetes, 2019. 68(Supplement 1): p. 1924-P.

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Peer Review #2 of "Rice koji reduced body weight gain, fat accumulation, and blood glucose level in high-fat diet-induced obese mice (v0.1)"

10.7287/peerj.540v0.1/reviews/2 ◽

2014 ◽

Keyword(s):

Body Weight ◽

Weight Gain ◽

Blood Glucose ◽

Blood Glucose Level ◽

Glucose Level ◽

High Fat Diet ◽

Body Weight Gain ◽

Obese Mice ◽

High Fat ◽

Reduced Body

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Ginkgo bilobaExtract Improves Insulin Signaling and Attenuates Inflammation in Retroperitoneal Adipose Tissue Depot of Obese Rats

Mediators of Inflammation ◽

10.1155/2015/419106 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Bruna Kelly Sousa Hirata ◽

Renata Mancini Banin ◽

Ana Paula Segantine Dornellas ◽

Iracema Senna de Andrade ◽

Juliane Costa Silva Zemdegs ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Insulin Signaling ◽

Metabolic Diseases ◽

Body Weight Gain ◽

Gene Expressions ◽

Akt Phosphorylation ◽

Reduced Body ◽

Obese Rats ◽

Fat Depot

Due to the high incidence and severity of obesity and its related disorders, it is highly desirable to develop new strategies to treat or even to prevent its development. We have previously described thatGinkgo bilobaextract (GbE) improved insulin resistance and reduced body weight gain of obese rats. In the present study we aimed to evaluate the effect of GbE on both inflammatory cascade and insulin signaling in retroperitoneal fat depot of diet-induced obese rats. Rats were fed with high fat diet for 2 months and thereafter treated for 14 days with 500 mg/kg of GbE. Rats were then euthanized and samples from retroperitoneal fat depot were used for western blotting, RT-PCR, and ELISA experiments. The GbE treatment promoted a significant reduction on both food/energy intake and body weight gain in comparison to the nontreated obese rats. In addition, a significant increase of both Adipo R1 and IL-10 gene expressions and IR and Akt phosphorylation was also observed, while NF-κB p65 phosphorylation and TNF-αlevels were significantly reduced. Our data suggest that GbE might have potential as a therapy to treat obesity-related metabolic diseases, with special interest to treat obese subjects resistant to adhere to a nutritional education program.

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