Essential Fatty Acids Linoleic Acid and α‐Linolenic Acid Sex‐Dependently Regulate Glucose Homeostasis in Obesity

Zhuang, Ping; Shou, Qiyang; Wang, Wenqiao; He, Lilin; Wang, Jun; Chen, Jingnan; Zhang, Yu; Jiao, Jingjing

doi:10.1002/mnfr.201800448

Cited by 32 publications

(21 citation statements)

References 51 publications

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“…Previous literature has also revealed a critical role of dietary factors, including dietary fat [5], in shaping gut microbial composition. Increased consumption of saturated fat induces intestinal dysbacteriosis and endotoxemia [6,7], whereas polyunsaturated fatty acids (PUFAs) restore gut micro-ecological equilibrium and relieve inflammation [8][9][10][11]. Notably, emerging evidence shows that marine n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are able to ameliorate insulin resistance (IR) in rodents probably via regulating adipocytokines secretion [12][13][14], inhibiting adipose remodeling [15], lowering inflammation [16][17][18], and enhancing mitochondrial function and β-oxidation [19].…”

Section: Introductionmentioning

confidence: 99%

Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice

et al. 2021

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Background Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to prevent the development of metabolic disorders. However, their individual role in treating hyperglycemia and the mechanism of action regarding gut microbiome and metabolome in the context of diabetes remain unclear. Results Supplementation of DHA and EPA attenuated hyperglycemia and insulin resistance without changing body weight in db/db mice while the ameliorative effect appeared to be more pronounced for EPA. DHA/EPA supplementation reduced the abundance of the lipopolysaccharide-containing Enterobacteriaceae whereas elevated the family Coriobacteriaceae negatively correlated with glutamate level, genera Barnesiella and Clostridium XlVa associated with bile acids production, beneficial Bifidobacterium and Lactobacillus, and SCFA-producing species. The gut microbiome alterations co-occurred with the shifts in the metabolome, including glutamate, bile acids, propionic/butyric acid, and lipopolysaccharide, which subsequently relieved β cell apoptosis, suppressed hepatic gluconeogenesis, and promoted GLP-1 secretion, white adipose beiging, and insulin signaling. All these changes appeared to be more evident for EPA. Furthermore, transplantation with DHA/EPA-mediated gut microbiota mimicked the ameliorative effect of DHA/EPA on glucose homeostasis in db/db mice, together with similar changes in gut metabolites. In vitro, DHA/EPA treatment directly inhibited the growth of Escherichia coli (Family Enterobacteriaceae) while promoted Coriobacterium glomerans (Family Coriobacteriaceae), demonstrating a causal effect of DHA/EPA on featured gut microbiota. Conclusions DHA and EPA dramatically attenuated hyperglycemia and insulin resistance in db/db mice, which was mediated by alterations in gut microbiome and metabolites linking gut to adipose, liver and pancreas. These findings shed light into the gut-organs axis as a promising target for restoring glucose homeostasis and also suggest a better therapeutic effect of EPA for treating diabetes.

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Section: Introductionmentioning

confidence: 99%

Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice

et al. 2021

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“…In recent years, a series of studies reported the effects of n-3 PUFAs or related carriers rich in n-3 PUFAs on the gut microbiota of animals or humans, including healthy volunteers (6), overweight individuals with metabolic syndrome (7), breast cancer survivors (8), mice with alcohol-induced liver injury (9), obese mice (4), early-life antibiotic exposure-induced obese mice (10), rats fed a high-fat diet (11), individuals with nonalcoholic fatty liver disease (12), and early-life-stress rats (13). Most of these studies focus on the effects of EPA and DHA on the gut microbiota of animals and humans with related diseases, and there are few reports on the effect of ALA monomers on the gut microbiota (14)(15)(16).…”

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confidence: 99%

Correlations between α-Linolenic Acid-Improved Multitissue Homeostasis and Gut Microbiota in Mice Fed a High-Fat Diet

et al. 2020

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Previous studies have shown that α-linolenic acid (ALA) has a significant regulatory effect on related disorders induced by high-fat diets (HFDs), but little is known regarding the correlation between the gut microbiota and disease-related multitissue homeostasis. We systematically investigated the effects of ALA on the body composition, glucose homeostasis, hyperlipidemia, metabolic endotoxemia and systemic inflammation, white adipose tissue (WAT) homeostasis, liver homeostasis, intestinal homeostasis, and gut microbiota of mice fed an HFD (HFD mice). We found that ALA improved HFD-induced multitissue metabolic disorders and gut microbiota disorders to various degrees. Importantly, we established a complex but clear network between the gut microbiota and host parameters. Several specific differential bacteria were significantly associated with improved host parameters. Rikenellaceae_RC9_gut_group and Parasutterella were positively correlated with HFD-induced “harmful indicators” and negatively correlated with “beneficial indicators.” Intriguingly, Bilophila showed a strong negative correlation with HFD-induced multitissue metabolic disorders and a significant positive correlation with most beneficial indicators, which is different from its previous characterization as a “potentially harmful genus.” Turicibacter might be the key beneficial bacterium for ALA-improved metabolic endotoxemia, while Blautia might play an important role in ALA-improved gut barrier integrity and anti-inflammatory effects. The results suggested that the gut microbiota, especially some specific bacteria, played an important role in the process of ALA-improved multitissue homeostasis in HFD mice, and different bacteria might have different divisions of regulation. IMPORTANCE Insufficient intake of n-3 polyunsaturated fatty acids is an important issue in modern Western-style diets. A large amount of evidence now suggests that a balanced intestinal microecology is considered an important part of health. Our results show that α-linolenic acid administration significantly improved the host metabolic phenotype and gut microbiota of mice fed a high-fat diet, and there was a correlation between the improved gut microbiota and metabolic phenotype. Some specific bacteria may play a unique regulatory role. Here, we have established correlation networks between gut microbiota and multitissue homeostasis, which may provide a new basis for further elucidating the relationship between the gut microbiota and host metabolism.

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“…Copper-fructose interaction-induced metabolic effects exhibit sex dimorphism (23,25). Sex speci c alterations of gut microbiota in response to a speci c diets have been demonstrated in a variety of studies (57)(58)(59). Given that the gut microbiota play a causal role in driving the development of metabolic diseases, we aimed to determine whether sex-speci c alterations of the gut microbiota are linked to hepatic steatosis.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Dietary Copper-Fructose Interaction-Induced Alterations of Gut Microbial Activity are Not Correlated to Hepatic Steatosis

Song

Fang

et al. 2020

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Abstract Background: Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the US. Diet copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner, and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods: Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6mg/kg and 1.5mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma ALT, AST and liver histology were evaluated. Fecal microbial contents were analyzed by 16S rRNA sequencing. Fecal and cecal short chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS).Results: Male and female rats exhibit similar trends of changes in the body weight, body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions: Our data demonstrated sex differences in the alterations of gut microbial activities and hepatic steatosis in response to dietary copper-fructose interaction in rats. Tissue-specific responses to dietary copper and fructose likely contribute to the sex differences in gut microbial activity and metabolic phenotype.

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Essential Fatty Acids Linoleic Acid and α‐Linolenic Acid Sex‐Dependently Regulate Glucose Homeostasis in Obesity

Abstract: Long-term intake of LA (for women) and ALA may have a protective effect on T2D development for obese/overweight subjects through sex-specific gut microbiota modulation and gut-adipose axis.

Cited by 32 publications

References 51 publications

Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice

Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice

Correlations between α-Linolenic Acid-Improved Multitissue Homeostasis and Gut Microbiota in Mice Fed a High-Fat Diet

Sex Differences in Dietary Copper-Fructose Interaction-Induced Alterations of Gut Microbial Activity are Not Correlated to Hepatic Steatosis

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