Mulberry leaves ameliorate obesity through enhancing brown adipose tissue activity and modulating gut microbiota

Author(s): Yao Sheng ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Junyu Liu ⁶ ^, ⁷ ^, ⁸ ^, ⁹ ^, ⁵ , Shujuan Zheng ⁶ ^, ⁷ ^, ⁸ ^, ⁹ ^, ⁵ , Fei Liang ¹⁰ ^, ¹¹ ^, ¹² ^, ⁵ , Yunbo Luo ⁶ ^, ⁷ ^, ⁸ ^, ⁹ ^, ⁵ , Kunlun Huang ⁶ ^, ⁷ ^, ⁸ ^, ⁹ ^, ⁵ , Wentao Xu ⁶ ^, ⁷ ^, ⁸ ^, ⁹ ^, ⁵ , Xiaoyun He ⁶ ^, ⁷ ^, ⁸ ^, ⁹ ^, ⁵

Publication date (Electronic): 2019

Journal: Food & Function

Publisher: Royal Society of Chemistry (RSC)

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Abstract

The increased prevalence of obesity significantly affects human health worldwide.

Abstract

The increased prevalence of obesity significantly affects human health worldwide. Improvement of glycometabolism by dietotherapy/herbal remedy is an effective approach to ameliorate obesity. In this study, high-fat-diet induced obese (DIO) mice were treated with mulberry leaves for 13 weeks. The results showed that mulberry leaves significantly alleviated adiposity of DIO mice including reducing body weight gain, fat accumulation and fasting blood glucose, and improving insulin sensitivity. In addition, mulberry leaves had protective effects on liver and kidneys. The abundant flavonoids, polyphenols and 1-deoxynojirimycin in mulberry leaves were likely responsible for their beneficial effects. Mechanistically, we found that mulberry leaves could alleviate obesity by enhancing brown adipose tissue (BAT) activity partly indicated by elevated thermogenesis and overexpression of uncoupling protein 1 in BAT. Moreover, mulberry leaves significantly increased the Bacteroidetes/ Firmicutes ratio and Akkermansia level that were closely associated with obesity development and progression, and decreased the potential proinflammatory Proteobacteria in feces. These findings reveal that the mulberry leaf is an edible plant food with therapeutic potential for obesity and may provide dietotherapy/herbal remedy to the treatment of obesity and its complications.

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Most cited references 32

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Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models.

E. Murphy, P. Cotter, S. Healy … (2010)

Increased efficiency of energy harvest, due to alterations in the gut microbiota (increased Firmicutes and decreased Bacteroidetes), has been implicated in obesity in mice and humans. However, a causal relationship is unproven and contributory variables include diet, genetics and age. Therefore, we explored the effect of a high-fat (HF) diet and genetically determined obesity (ob/ob) for changes in microbiota and energy harvesting capacity over time. Seven-week-old male ob/ob mice were fed a low-fat diet and wild-type mice were fed either a low-fat diet or a HF-diet for 8 weeks (n=8/group). They were assessed at 7, 11 and 15 weeks of age for: fat and lean body mass (by NMR); faecal and caecal short-chain fatty acids (SCFA, by gas chromatography); faecal energy content (by bomb calorimetry) and microbial composition (by metagenomic pyrosequencing). A progressive increase in Firmicutes was confirmed in both HF-fed and ob/ob mice reaching statistical significance in the former, but this phylum was unchanged over time in the lean controls. Reductions in Bacteroidetes were also found in ob/ob mice. However, changes in the microbiota were dissociated from markers of energy harvest. Thus, although the faecal energy in the ob/ob mice was significantly decreased at 7 weeks, and caecal SCFA increased, these did not persist and faecal acetate diminished over time in both ob/ob and HF-fed mice, but not in lean controls. Furthermore, the proportion of the major phyla did not correlate with energy harvest markers. The relationship between the microbial composition and energy harvesting capacity is more complex than previously considered. While compositional changes in the faecal microbiota were confirmed, this was primarily a feature of high-fat feeding rather than genetically induced obesity. In addition, changes in the proportions of the major phyla were unrelated to markers of energy harvest which changed over time. The possibility of microbial adaptation to diet and time should be considered in future studies.

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Human intestinal microbiota composition is associated with local and systemic inflammation in obesity.

Froukje Verdam, Susana Fuentes, Charlotte de Jonge … (2013)

Intestinal microbiota have been suggested to contribute to the development of obesity, but the mechanism remains elusive. The relationship between microbiota composition, intestinal permeability, and inflammation in nonobese and obese subjects was investigated. Fecal microbiota composition of 28 subjects (BMI 18.6-60.3 kg m(-2) ) was analyzed by a phylogenetic profiling microarray. Fecal calprotectin and plasma C-reactive protein levels were determined to evaluate intestinal and systemic inflammation. Furthermore, HbA1c , and plasma levels of transaminases and lipids were analyzed. Gastroduodenal, small intestinal, and colonic permeability were assessed by a multisaccharide test. Based on microbiota composition, the study population segregated into two clusters with predominantly obese (15/19) or exclusively nonobese (9/9) subjects. Whereas intestinal permeability did not differ between clusters, the obese cluster showed reduced bacterial diversity, a decreased Bacteroidetes/Firmicutes ratio, and an increased abundance of potential proinflammatory Proteobacteria. Interestingly, fecal calprotectin was only detectable in subjects within the obese microbiota cluster (n = 8/19, P = 0.02). Plasma C-reactive protein was also increased in these subjects (P = 0.0005), and correlated with the Bacteroidetes/Firmicutes ratio (rs = -0.41, P = 0.03). Intestinal microbiota alterations in obese subjects are associated with local and systemic inflammation, suggesting that the obesity-related microbiota composition has a proinflammatory effect. Copyright © 2013 The Obesity Society.

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The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation.

J Picot, J. Jones, JL Colquitt … (2009)

To assess the clinical effectiveness and cost-effectiveness of bariatric surgery for obesity. Seventeen electronic databases were searched [MEDLINE; EMBASE; PreMedline In-Process & Other Non-Indexed Citations; The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, DARE, NHS EED and HTA databases; Web of Knowledge Science Citation Index (SCI); Web of Knowledge ISI Proceedings; PsycInfo; CRD databases; BIOSIS; and databases listing ongoing clinical trials] from inception to August 2008. Bibliographies of related papers were assessed and experts were contacted to identify additional published and unpublished references. Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text using a standard form. Interventions investigated were open and laparoscopic bariatric surgical procedures in widespread current use compared with one another and with non-surgical interventions. Population comprised adult patients with body mass index (BMI) > or = 30 and young obese people. Main outcomes were at least one of the following after at least 12 months follow-up: measures of weight change; quality of life (QoL); perioperative and postoperative mortality and morbidity; change in obesity-related comorbidities; cost-effectiveness. Studies eligible for inclusion in the systematic review for comparisons of Surgery versus Surgery were RCTs. For comparisons of Surgery versus Non-surgical procedures eligible studies were RCTs, controlled clinical trials and prospective cohort studies (with a control cohort). Studies eligible for inclusion in the systematic review of cost-effectiveness were full cost-effectiveness analyses, cost-utility analyses, cost-benefit analyses and cost-consequence analyses. One reviewer performed data extraction, which was checked by two reviewers independently. Two reviewers independently applied quality assessment criteria and differences in opinion were resolved at each stage. Studies were synthesised through a narrative review with full tabulation of the results of all included studies. In the economic model the analysis was developed for three patient populations, those with BMI > or = 40; BMI > or = 30 and or = 30 and or = 30 and 40, ICERs were 18,930 pounds at two years and 1397 pounds at 20 years, and for BMI > or = 30 and < 35, ICERs were 60,754 pounds at two years and 12,763 pounds at 20 years. Deterministic and probabilistic sensitivity analyses produced ICERs which were generally within the range considered cost-effective, particularly at the long twenty year time horizons, although for the BMI 30-35 group some ICERs were above the acceptable range. Bariatric surgery appears to be a clinically effective and cost-effective intervention for moderately to severely obese people compared with non-surgical interventions. Uncertainties remain and further research is required to provide detailed data on patient QoL; impact of surgeon experience on outcome; late complications leading to reoperation; duration of comorbidity remission; resource use. Good-quality RCTs will provide evidence on bariatric surgery for young people and for adults with class I or class II obesity. New research must report on the resolution and/or development of comorbidities such as Type 2 diabetes and hypertension so that the potential benefits of early intervention can be assessed.

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Author and article information

Journal

Journal ID (publisher-id): FFOUAI

Title: Food & Function

Abbreviated Title: Food Funct.

Publisher: Royal Society of Chemistry (RSC)

ISSN (Print): 2042-6496

ISSN (Electronic): 2042-650X

Publication date Created: August 14 2019

Publication date (Electronic): 2019

Volume: 10

Issue: 8

Pages: 4771-4781

Affiliations

[1 ]Shanghai Institute for Advanced Immunochemical Studies

[2 ]ShanghaiTech University

[3 ]Shanghai

[4 ]201210

[5 ]China

[6 ]Beijing Advanced Innovation Center for Food Nutrition and Human Health

[7 ]College of Food Science and Nutritional Engineering

[8 ]China Agricultural University

[9 ]Beijing

[10 ]Department of Reproductive Physiology

[11 ]Zhejiang Academy of Medical Sciences

[12 ]Hangzhou

Article

DOI: 10.1039/C9FO00883G

PubMed ID: 31312821

SO-VID: e392cc3d-33bc-4f45-b8f5-012ad4f732fc

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Mulberry leaves ameliorate obesity through enhancing brown adipose tissue activity and modulating gut microbiota

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Most cited references 32

Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models.

Human intestinal microbiota composition is associated with local and systemic inflammation in obesity.

The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation.

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