Inulin ameliorates metabolic syndrome in high-fat diet-fed mice by regulating gut microbiota and bile acid excretion

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Abstract

Background: Inulin is a natural plant extract that improves metabolic syndrome by modulating the gut microbiota. Changes in the gut microbiota may affect intestinal bile acids. We suggest that inulin may improve metabolism by inducing bile acid excretion by gut microbes.

Methods: Male C57/BL mice were fed either a high-fat diet (60% calories) or a regular diet for 16 weeks, with oral inulin (10% w/w). At the end of the experiment, the gene expression levels (FGF15, CD36, Srebp-1c, FASN, and ACC) in the liver and intestines, as well as the serum levels of triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, total cholesterol, and free fatty acids, were collected. The expression of FGF15 was examined using Western blot analysis. The fat distribution in the liver and groin was detected by oil red and hematoxylin and eosin staining. Simultaneously, the levels of serum inflammatory factors (alanine aminotransferase and aspartate aminotransferase) were detected to explore the side effects of inulin.

Results: Inulin significantly improved glucose tolerance and insulin sensitivity, and decreased body weight and serum TG and LDL levels, in mice fed normal diet. Furthermore, inulin increased the α-diversity of the gut microbiota and increased the fecal bile acid and TG excretion in inulin-treated mice. In addition, inulin significantly reduced lipid accumulation in liver and inguinal fat, white fat weight, and hepatic steatosis. Western blot analysis showed that inulin reduced the expression of FGF15, a bile acid reabsorption protein.

Conclusion: Inulin ameliorates the glucose and lipid metabolic phenotypes of mice fed a normal diet, including decreased intestinal lipid absorption, increased glucose tolerance, increased insulin sensitivity, and decreased body weight. These changes may be caused by an increase in bile acid excretion resulting from changes in the gut microbiota that affect intestinal lipid absorption.

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Most cited references 34

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Global Perspectives on Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis

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Over the past 2 decades, nonalcoholic fatty liver disease (NAFLD) has grown from a relatively unknown disease to the most common cause of chronic liver disease in the world. In fact, 25% of the world's population is currently thought to have NAFLD. Nonalcoholic steatohepatitis (NASH) is the subtype of NAFLD that can progress to cirrhosis, hepatocellular carcinoma (HCC), and death. NAFLD and NASH are not only found in adults-there is also a high prevalence of these diseases in children and adolescents. Because of the close association of NAFLD with type 2 diabetes (T2DM) and obesity, the latest models predict that the prevalence of NAFLD and NASH will increase, causing a tremendous clinical and economic burden and poor patient-reported outcomes. Nonetheless, there is no accurate noninvasive method to detect NASH, and treatment of this disease is limited to lifestyle modifications. To examine the state of NAFLD among different regions and understand the global trajectory of this disease, an international group of experts came together during the 2017 American Association for the Study of Liver Diseases Global NAFLD Forum. We provide a summary of this forum and an assessment of the current state of NAFLD and NASH worldwide.

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Global burden of obesity in 2005 and projections to 2030.

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To estimate the overall prevalence and absolute burden of overweight and obesity in the world and in various regions in 2005 and to project the global burden in 2030. Pooling analysis. We identified sex- and age-specific prevalence of overweight and obesity in representative population samples from 106 countries, which cover approximately 88% of the world population, using MEDLINE and other computerized databases, supplemented by a manual search of references from retrieved articles. Sex- and age-specific prevalence of overweight and obesity were applied to the 2005 population to estimate the numbers of overweight and obese individuals in each country, each world region and the entire world. In addition, the prevalence, with and without adjusting for secular trends, were applied to the 2030 population projections to forecast the number of overweight and obese individuals in 2030. Overall, 23.2% (95% confidence interval 22.8-23.5%) of the world's adult population in 2005 was overweight (24.0% in men (23.4-24.5%) and 22.4% in women (21.9-22.9%)), and 9.8% (9.6-10.0%) was obese (7.7% in men (7.4-7.9%) and 11.9% in women (11.6-12.2%)). The estimated total numbers of overweight and obese adults in 2005 were 937 million (922-951 million) and 396 million (388-405 million), respectively. By 2030, the respective number of overweight and obese adults was projected to be 1.35 billion and 573 million individuals without adjusting for secular trends. If recent secular trends continue unabated, the absolute numbers were projected to total 2.16 billion overweight and 1.12 billion obese individuals. Overweight and obesity are important clinical and public health burdens worldwide. National programs for the prevention and treatment of overweight, obesity and related comorbidities and mortalities should be a public health priority.

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Elizabeth Brunt, Vincent W. S. Wong, Valerio Nobili … (2015)

Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring.

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Author and article information

Contributors

Qitong Fan: URI : https://loop.frontiersin.org/people/2231607/overview

Journal

Journal ID (nlm-ta): Front Pharmacol

Journal ID (iso-abbrev): Front Pharmacol

Journal ID (publisher-id): Front. Pharmacol.

Title: Frontiers in Pharmacology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1663-9812

Publication date (Electronic): 24 July 2023

Publication date Collection: 2023

Volume: 14

Electronic Location Identifier: 1226448

Affiliations

[1] ¹ Department of Gastrointestinal Surgery , Affiliated Hospital of Putian University , Putian, China

[2] ² Department of Bariatric Surgery , The First Affiliated Hospital of Jinan University , Guangzhou, China

[3] ³ Department of Anaesthesia , The First Hospital of Putian City , Putian, Fujian, China

[4] ⁴ The Department of General Surgery , The First Affiliated Hospital of Gannan Medical University , Ganzhou, Jiangxi, China

[5] ⁵ Department of General Practice , Affiliated Hospital of Putian University , Putian, China

[6] ⁶ Department of Human Anatomy , Nanchang University Fuzhou Medical College , Fuzhou, China

Author notes

Edited by: Yong Gao, Guangzhou University of Chinese Medicine, China

Reviewed by: Denglang Zou, Qinghai Normal University, China

Chenglin Han, Tongji Hospital Affiliated to Tongji University, China

*Correspondence: Limei Ni, ytnlm@ 123456163.com ; Qitong Fan, qitong_f@ 123456163.com

[ † ]

These authors have contributed equally to this work

Article

Publisher ID: 1226448

DOI: 10.3389/fphar.2023.1226448

PMC ID: 10404850

PubMed ID: 37554983

SO-VID: 8c3533d4-d50b-41db-8c8d-7422bc0d5c40

License:

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