The expanding area of health benefits of brassica vegetables

Zhao, Anqi

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https://hdl.handle.net/2142/120518 Copy

Description

Title

The expanding area of health benefits of brassica vegetables

Author(s)

Zhao, Anqi

Issue Date

2023-04-21

Director of Research (if dissertation) or Advisor (if thesis)

Miller, Michael

Doctoral Committee Chair(s)

Pepino, Yanina

Committee Member(s)

• Pan, Yuan-Xiang
• Sirk, Shannon

Department of Study

Nutritional Sciences

Discipline

Nutritional Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

brassica vegetable, isothiocyanate, microbiota, microbial metabolism, GLP-1, obesity

Abstract

Brassica vegetables are a rich source of glucosinolates (GSLs), a group of sulfur-containing compounds that are relatively unique to these vegetables (broccoli, kale, and others). Upon hydrolysis, GSLs can be converted to bioactive isothiocyanates (ITCs), which are thought to be responsible for many of their health benefits. When consumed raw, GSLs can be converted to ITCs by the plant enzyme myrosinase. Heat (cooking) inactivates myrosinase, then gut microbiota become responsible for any GSL conversion to ITCs. The variation in individual’s gut microbiota can lead to large variability (< 1% – 40%) in GSL conversion to ITC. To date, little is known about microbial GSL metabolism in the mammalian gut. The recent discovery of bitter-taste receptors (T2Rs) in the gut, their involvement in GLP-1 secretion and the ability of ITCs to be T2R ligands, opens new potential for discoveries of health benefits of brassica. GLP-1 is intimately involved in glucose regulation and satiety, two health issues that are of major concern for the US population. We hypothesize that ITCs bind intestinal T2R(s) to trigger GLP-1-dependent control of obesity and glucose tolerance. Optimizing microbial ITC production in the gut, both amount and location produced, has the potential to prevent or reverse glucose intolerance and obesity in humans. Our central hypothesis is that frequent brassica ingestion alters the gut microbiota resulting in increased ITC production in situ. Concomitantly, this results in increased gut T2R activation and GLP-1 secretion, and is thus expected to improve glucose homeostasis and control weight gain. We first showed a variety of ITCs, including allyl isothiocyanate (AITC), sulforaphane (SF), phenethyl isothiocyanate (PEITC), and benzyl isothiocyanate (BITC), increased intracellular calcium flux and induced GLP-1 secretion from STC-1 cells (Chapter 2). These impacts are abolished by addition of calcium flux inhibitors (T2R pathway inhibitors) and TRPA1 channel antagonists. Knockdown of TRPA1 impaired AITC- and SF- induced GLP-1 secretion, whereas knockdown of Tas2r138 impaired AITC-induced GLP-1 secretion but not SF. Findings suggest that ITCs induce GLP-1 secretion from STC-1 cells, through activating TRPA1 and various T2Rs. Next, we evaluated the impacts of cooked broccoli consumption on microbial metabolism of GSL in lean and obese mice (Chapter 3). Seven-day cooked-broccoli consumption increased ex vivo microbial glucoraphanin (GRP, the major GSL in broccoli) hydrolysis by mouse cecal contents, led to more production of SF, sulforaphane-cysteine (SF-CYS), and total ITC, also increased colonic NQO1 activity. Cecal microbiota composition and potential correlation between microbiota and GRP metabolites were evaluated. Our findings suggest that cooked broccoli consumption enhanced microbial GRP hydrolysis to produce more bioactive ITCs, regardless of the host body composition (lean vs obese). Characterization of ex vivo GRP metabolites and cecal microbiota composition provided information for understanding microbial metabolism of GRP in lean and obese host. Knowing that ITCs interact with intestinal bitter-tasting compound sensors to trigger GLP-1 secretion in the gut, and frequent cooked broccoli consumption leads to increased ITC production in the gut, we then moved forward to test the potential of broccoli/dietary GRP consumption in ameliorating obesity (Chapter 4). Furthermore, we tested the hypothesis that the physiological impacts of broccoli/ dietary GRP on obesity is through a T2R and/or GLP-1 involved manner. We examined broccoli (raw and cooked) and dietary glucoraphanin (GRP) on regulating body weight, glucose metabolism, and lipid profile in diet-induced obese (DIO) mice. Forty DIO mice at age of 16 weeks old were fed with raw broccoli (HF-RB), cooked broccoli (HF-CB), GRP (HF-GRP), or high-fat diet (HFD). At the end of 4-week intervention, DIO mice fed with HF-RB had less weight gain, compared to the control group (HFD) or HF-CB/HF-GRP groups (p < 0.05). In addition, 4-week HF-RB feeding reduced fasting blood LDL/VLDL levels compared to HFD (p < 0.05). A trend of increase in glucagon-like peptide 1 (GLP-1) gene expression in the duodenum in mice fed with HF-RB (p < 0.1) and increased Tas2r105 expression in the colon in mice fed with HF-GRP (p < 0.05) were observed. These data suggest that 4-week raw broccoli supplementation may ameliorate body weight gain and improve lipid profile in DIO mice, and broccoli/GRP consumption, regardless of presence of active plant myrosinase, has the potential of interacting with intestinal T2Rs to induce GLP-1 secretion.

Graduation Semester

2023-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2023 Anqi Zhao

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