Salvianolic Acid B Inhibited PPARγ Expression and Attenuated Weight Gain in Mice with High-Fat Diet-Induced Obesity

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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Helminth infection modulates number and function of adipose tissue Tregs in high fat diet-induced obesity

10.1101/2021.12.20.473610 ◽

2021 ◽

Author(s):

Camila Queiroz-Glauss ◽

Mariana Vieira ◽

Marcela Helena Gonçalves-Pereira ◽

Stephanie Almeida ◽

Rachel Freire ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

High Fat Diet ◽

Metabolic Diseases ◽

Experimental Studies ◽

Treg Cells ◽

Loss Of Function ◽

High Fat ◽

Diet Induced Obesity ◽

And Function

Background: Epidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms induced by the parasite that regulate the development of metabolic diseases in the host are unclear. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity. Principal Findings: The presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by higher levels of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also revert the loss of function in Tregs associated with high fat diet. Conclusion: These data suggest that H. polygyrus infection can prevent weight gain and metabolic syndrome in animals fed with high fat diet associated with modulations of adipose tissue Treg cells.

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Estradiol and high fat diet associate with changes in gut microbiota in female ob/ob mice

Scientific Reports ◽

10.1038/s41598-019-56723-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Kalpana D. Acharya ◽

Xing Gao ◽

Elizabeth P. Bless ◽

Jun Chen ◽

Marc J. Tetel

Keyword(s):

Weight Gain ◽

Gut Microbiota ◽

High Fat Diet ◽

Energy Homeostasis ◽

Low Grade ◽

High Fat ◽

Diet Induced Obesity ◽

Increased Risk ◽

17Β Estradiol ◽

Low Grade Inflammation

AbstractEstrogens protect against diet-induced obesity in women and female rodents. For example, a lack of estrogens in postmenopausal women is associated with an increased risk of weight gain, cardiovascular diseases, low-grade inflammation, and cancer. Estrogens act with leptin to regulate energy homeostasis in females. Leptin-deficient mice (ob/ob) exhibit morbid obesity and insulin resistance. The gut microbiome is also critical in regulating metabolism. The present study investigates whether estrogens and leptin modulate gut microbiota in ovariectomized ob/ob (obese) or heterozygote (lean) mice fed high-fat diet (HFD) that received either 17β-Estradiol (E2) or vehicle implants. E2 attenuated weight gain in both genotypes. Moreover, both obesity (ob/ob mice) and E2 were associated with reduced gut microbial diversity. ob/ob mice exhibited lower species richness than control mice, while E2-treated mice had reduced evenness compared with vehicle mice. Regarding taxa, E2 was associated with an increased abundance of the S24-7 family, while leptin was associated with increases in Coriobacteriaceae, Clostridium and Lactobacillus. Some taxa were affected by both E2 and leptin, suggesting these hormones alter gut microbiota of HFD-fed female mice. Understanding the role of E2 and leptin in regulating gut microbiota will provide important insights into hormone-dependent metabolic disorders in women.

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Salvianolic Acid B Protects Against Fatty Acid-Induced Renal Tubular Injury via Inhibition of Endoplasmic Reticulum Stress

Frontiers in Pharmacology ◽

10.3389/fphar.2020.574229 ◽

2020 ◽

Vol 11 ◽

Author(s):

Xiaoyi Mai ◽

Xin Yin ◽

Peipei Chen ◽

Minzhou Zhang

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

High Fat Diet ◽

Salvianolic Acid B ◽

Tubular Injury ◽

High Fat ◽

Salvianolic Acid ◽

Renal Tubular ◽

Hk2 Cells

Background/Aims: Obesity-related kidney disease is associated with elevated levels of saturated free fatty acids (SFA). SFA lipotoxicity in tubular cells contributes to significant cellular apoptosis and injury. Salvianolic acid B (SalB) is the most abundant bioactive molecule from Radix Salviae Miltiorrhizae. In this study, we investigated the effect of SalB on SFA-induced renal tubular injury and endoplasmic reticulum (ER) stress, in vivo and in vitro.Methods: C57BL/6 mice were assigned to five groups: a control group with normal diet (Nor), high-fat diet group (HFD), and HFD with three different SalB treatment doses, low (SalBL; 3 mg/kg), medium (SalBM; 6.25 mg/kg), and high (SalBH; 12.5 mg/kg) doses. SalB was intraperitoneally injected daily for 4 weeks after 8 weeks of HFD. After 12 weeks, mice were sacrificed and kidneys and sera were collected. Apoptosis and ER stress were induced in human proximal tubule epitelial (HK2) cells by palmitic acid (PA, 0.6 mM), tunicamycin (TM, 1 μg/ml), or thapsigargin (TG, 200 nM) in vitro.Results: C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks exhibited increased apoptosis (Bax and cleaved caspase-3) and ER stress (BIP, P-eIF2α, ATF4, CHOP, ATF6, IRE1α, and XBP1s) markers expression in the kidney, compared with control mice, which were remarkably suppressed by SalB treatment. In vitro studies showed that PA (0.6 mM) induced apoptosis and ER stress in cultured HK2 cells. SalB treatment attenuated all the adverse effects of PA. However, SalB failed to inhibit TM or TG-induced ER stress in HK2 cells.Conclusion: The study indicated that SalB may play an important role in obesity-related kidney injury via mediating SFA-induced ER stress.

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Estradiol modulates gut microbiota in female ob/ob mice fed a high fat diet

10.1101/612283 ◽

2019 ◽

Author(s):

Kalpana D Acharya ◽

Xing Gao ◽

Elizabeth P Bless ◽

Jun Chen ◽

Marc J Tetel

Keyword(s):

Weight Gain ◽

Gut Microbiota ◽

Gut Microbiome ◽

High Fat Diet ◽

Energy Homeostasis ◽

High Fat ◽

Diet Induced Obesity ◽

The Family ◽

Satiety Hormone ◽

17Β Estradiol

AbstractEstrogens protect against diet-induced obesity in women and female rodents. In support of these anorectic effects, lack of estrogens in postmenopausal women is associated with weight gain, increasing their risk for cardiovascular diseases and cancer. Estrogens act with leptin, a satiety hormone encoded by the ob gene, to regulate energy homeostasis in females. Leptin-deficient mice (ob/ob) exhibit morbid obesity and insulin resistance. In addition to estrogens and leptin, the gut microbiome (gut microbes and their metabolites), is critical in regulating energy metabolism. The present study investigates whether estrogens and leptin modulate gut microbiota in ovariectomized ob/ob (obese) or heterozygote (lean) control mice fed a high-fat diet (HFD) that received either 17β-Estradiol (E2) or vehicle implants. E2 attenuated weight gain in both genotypes compared to vehicle counterparts. Moreover, both obesity (ob/ob mice) and E2 reduced gut microbial diversity. ob/ob mice exhibited lower species richness than control mice, while E2-treated mice had reduced evenness compared to vehicle mice. Regarding taxa, E2 treatment was associated with higher abundances of the family S24-7. Leptin was associated with higher abundances of Coriobacteriaceae, Clostridium and Lactobacillus. E2 and leptin had overlapping effects on relative abundances of some taxa, suggesting that interaction of these hormones is important in gut microbial homeostasis. Taken together, these findings suggest that E2 and leptin profoundly alter the gut microbiota of HFD-fed female mice. Understanding the function of E2 and leptin in regulating gut microbiota will allow the development of therapies targeting the gut microbiome for hormone-dependent metabolic disorders in women.

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The Molecular Effects of a High Fat Diet on Endometrial Tumour Biology

Life ◽

10.3390/life10090188 ◽

2020 ◽

Vol 10 (9) ◽

pp. 188

Author(s):

Michael Wilkinson ◽

Piriyah Sinclair ◽

Ludmilla Dellatorre-Teixeira ◽

Patrick Swan ◽

Eoin Brennan ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Weight Gain ◽

Rat Model ◽

High Fat Diet ◽

Cancer Metastasis ◽

Chow Diet ◽

Suitable Model ◽

High Fat ◽

Diet Induced Obesity

We sought to validate the BDII/Han rat model as a model for diet-induced obesity in endometrial cancer (EC) and determine if transcriptomic changes induced by a high fat diet (HFD) in an EC rat model can be used to identify novel biomarkers in human EC. Nineteen BDII/Han rats were included. Group A (n = 7) were given ad lib access to a normal calorie, normal chow diet (NCD) while Group B (n = 12) were given ad lib access to a calorie rich HFD for 15 months. RNAseq was performed on endometrial tumours from both groups. The top-ranking differentially expressed genes (DEGs) were examined in the human EC using The Cancer Genome Atlas (TCGA) to assess if the BDII/Han rat model is an appropriate model for human obesity-induced carcinogenesis. Weight gain in HFD rats was double the weight gain of NCD rats (50 g vs. 25 g). The incidence of cancer was similar in both groups (4/7—57% vs. 4/12—33%; p = 0.37). All tumours were equivalent to a Stage 1A, Grade 2 human endometrioid carcinoma. A total of 368 DEGs were identified between the tumours in the HFD group compared to the NCD group. We identified two upstream regulators of the DEGs, mir-33 and Brd4, and a pathway analysis identified downstream enrichment of the colorectal cancer metastasis and ovarian cancer metastasis pathways. Top-ranking DEGs included Tex14, A2M, Hmgcs2, Adamts5, Pdk4, Crabp2, Capn12, Npw, Idi1 and Gpt. A2M expression was decreased in HFD tumours. Consistent with these findings, we found a significant negative correlation between A2M mRNA expression levels and BMI in the TCGA cohort (Spearman’s Rho = −0.263, p < 0.001). A2M expression was associated with improved overall survival (HR = 0.45, 95% CI 0.23–0.9, p = 0.024). Crabp2 expression was increased in HFD tumours. In human EC, CRABP2 expression was associated with reduced overall survival (HR = 3.554, 95% CI 1.875–6.753, p < 0.001). Diet-induced obesity can alter EC transcriptomic profiles. The BDII/Han rat model is a suitable model of diet-induced obesity in endometrial cancer and can be used to identify clinically relevant biomarkers in human EC.

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Time-restricted feeding on weekdays restricts weight gain: A study using rat models of high-fat diet-induced obesity

Physiology & Behavior ◽

10.1016/j.physbeh.2017.02.032 ◽

2017 ◽

Vol 173 ◽

pp. 298-304 ◽

Cited By ~ 17

Author(s):

Magnus Kringstad Olsen ◽

Man Hung Choi ◽

Bård Kulseng ◽

Chun-Mei Zhao ◽

Duan Chen

Keyword(s):

Weight Gain ◽

High Fat Diet ◽

Restricted Feeding ◽

High Fat ◽

Rat Models ◽

Diet Induced Obesity

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Weight Loss in Response to Food Deprivation Predicts The Extent of Diet Induced Obesity in C57BL/6J Mice

10.1101/004283 ◽

2014 ◽

Author(s):

Matthew J. Peloqiun ◽

Dave Bridges

Keyword(s):

Weight Loss ◽

Weight Gain ◽

Food Deprivation ◽

High Fat Diet ◽

Control Diet ◽

Chow Diet ◽

High Fat ◽

Strong Negative Correlation ◽

Diet Induced Obesity ◽

Serum Hormone

Inbred C57BL/6J mice have been used to study diet-induced obesity and the detrimental physiological effects associated with it. Little is understood about predictive factors that predispose an animal to weight gain. To address this, mice were fed a high fat diet, control diet or normal chow diet. Several measurements including pre-diet serum hormone levels and pre-diet body weight were analyzed, but these had limited predictive value regarding weight gain. However, baseline measurements of weight loss in response to food deprivation showed a strong negative correlation with high fat diet-induced weight gain. These data suggest that fasting-induced weight loss in adolescent mice is a useful predictor of diet-induced weight gain.

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Differential sensitivity of chronic high-fat-diet-induced obesity in Sprague-Dawley rats

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2017-0030 ◽

2018 ◽

Vol 29 (5) ◽

pp. 553-563 ◽

Cited By ~ 2

Author(s):

Shakthi R.K. Devan ◽

Surendar Arumugam ◽

Ganesh Shankar ◽

Suresh Poosala

Keyword(s):

Body Weight ◽

Weight Gain ◽

High Fat Diet ◽

Body Weight Gain ◽

Differential Sensitivity ◽

Sprague Dawley ◽

High Fat ◽

Diet Induced Obesity ◽

High Fat Diets ◽

Fat Diets

AbstractBackgroundThe prevalence of obesity is reported to be increasing owing to the high intake of dietary fat and is a predisposing risk factor with associated complex metabolic syndromes in the human population. Preclinical rodent models play a pivotal role in understanding the pathogenesis of obesity and development of new treatment strategies for humans. High-fat-diet (HFD)-induced rodents are used for chronic obesity models owing to their quick adaptation to high-fat diets and rapid body weight gain and different rats (Wistar Sprague-Dawley and Lewis) have been used by various researchers. However, the selection of appropriate stock contributes to the translation of clinically linked disease phenotypes to preclinical animal models.MethodsThe study was conducted using two commonly used rat stocks Hsd:Sprague-Dawley (SD) and Crl:Charles River (CD) to develop a chronic high-fat-diet-induced obesity model (DIO) to explore the underlying mechanisms of obesity and its utilization in drug discovery and development during preclinical stages. In addition two high-fat diets of different composition were evaluated (D12327; 40% kcal fat and D12492; 60% kcal fat) for their potential to induce obesity using these two stocks.ResultsA differential sensitivity to HFD was observed in body weight gain fat mass composition and obesity-linked symptoms such as impaired glucose tolerance insulin and leptin levels. The comparative research findings of Hsd:SD and Crl:CD rat stocks suggested that Crl:CD rats are more prone to diet-induced obesity and its associated complications.ConclusionsCrl:CD rats were found to be a suitable model for obesity over Hsd:SD when considering the important hallmarks of metabolic disorders that may be utilized for obesity-related research.

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Differential effects of diet and weight on taste responses in diet-induced obese mice

10.1101/564211 ◽

2019 ◽

Cited By ~ 2

Author(s):

Zachary C. Ahart ◽

Laura E. Martin ◽

Bailey R. Kemp ◽

Debarghya Dutta Banik ◽

Stefan G.E. Roberts ◽

...

Keyword(s):

Weight Gain ◽

High Fat Diet ◽

Taste Perception ◽

Obese Mice ◽

High Fat ◽

Taste System ◽

Obesity Epidemic ◽

Diet Induced Obesity ◽

Underlying Mechanisms ◽

The Relationship

AbstractThe ever growing obesity epidemic has created a need to develop a better understanding of the underlying mechanisms responsible for this condition. Appetite and consumption are directly influenced by the taste system which determines if potential food items will be ingested or rejected. While previous studies have reported that obese individuals have reduced taste perception, the relationship between these processes is still poorly understood. Earlier work has demonstrated that diet-induced obesity (DIO) directly impairs taste responses, particularly for sweet stimuli. These deficits occurred in the cells located in the oral cavity as well as in the behavioral responses. However, it is not clear if these changes to the taste system are due to obesity or to the high fat diet exposure. The goal of the current study was to determine if diet or excess weight is responsible for the DIO induced taste deficits. Using a combination of live cell imaging, brief-access licking, immunohistochemistry and real-time PCR, we have found that diet and weight gain can each selectivity affect taste. Follow up experiments determined that two key signaling proteins, gustducin and phospholipase Cβ2, are significantly reduced in the high fat diet without weight gain and obese mice, identifying a potential mechanism for the reduced taste responsiveness to some stimuli. Our data indicate that the relationship between obesity and taste is complex and reveal that for some stimuli, diet alone can cause taste deficits, even without the onset of obesity.

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