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

Abstract

estrogens 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. Estrogens profoundly influence energy homeostasis 1-3 , as well as reproductive physiology and behavior 4-6. Estrogens reduce food intake, attenuate body weight gain and adiposity, and increase physical activity in humans and rodents 1,2. Postmenopausal women have lower levels of circulating estrogens and an increased tendency to gain fat weight, which increases their risk for obesity, cardiovascular disease, stroke, and type 2 diabetes 7-9. Similarly, in mice on a high-fat diet (HFD), ovariectomy increases energy intake and obesity, while estradiol (E2) treatment prevents weight gain 2,10-13 , indicating that estrogens protect against HFD-induced obesity. Leptin is a peptide hormone secreted primarily by adipocytes, which acts primarily in the brain to stimulate metabolism, promote satiety, and regulate fat storage 14-16. A mutation in the ob gene that encodes leptin results in mice lacking the hormone (ob/ob) 17. While phenotypically normal at birth, ob/ob mice quickly develop obesity and diabetes 18. Additionally, ob/ob mice exhibit increased food intake and decreased physical activity, energy metabolism, and body temperature compared to lean controls, making ob/ob mice an excellent genetic model of obesity 19-21. Administering leptin to adult ob/ob mice reverses these effects by decreasing food intake, increasing energy output and decreasing circulating levels of glucose and insulin 19,22. Leptin and estrogen signaling pathways interact to influence reproduction and energy metabolism. High levels of E2 are associated with increased leptin sensitivity in both male and female rodents 23. In contrast, decreased estrogens in ovar...

Selective Estrogen Receptor Modulator Lasofoxifene Suppresses Spondyloarthritis Manifestation and Affects Characteristics of Gut Microbiota in Zymosan-induced SKG Mice

“…Our study was consistent with other studies showed that estradiol supplementation showed signi cantly lower level of the F/B ratio compared with control group in a male mouse of colorectal cancer model [27]. E2 treatment increased the relative abundance of Bacteroidetes in leptinde cient mice [28]. Rogier et al [29] reported that the intestinal microbiota of naïve mice was dominated by the phylum Bacteroidetes.…”

“…E2 or Laso treatment altered β-diversity, but there was no signi cant difference between zymosan + E2 treated group and zymosan + Laso treated group. A previous study showed that E2 treatment was associated with lower species evenness and E2 treatment also effect on β-diversity in leptin-de cient mice [28]. In male mice of colorectal cancer model, α-diversity, observed OTU count, was increased in E2 supplemented male.…”

Metformin Strongly Affects Gut Microbiome Composition in High-Fat Diet-Induced Type 2 Diabetes Mouse Model of Both Sexes

“…In addition, several studies, which have investigated sex-related differences in the gut microbiome in the context of changed diet, have identified hormonal effects on gut microbiome composition ( 33 – 35 )⁠, specifically emphasizing estrogen-induced gut microbiome changes and protection against metabolic syndrome in mice, both of the C57BL/6 and ob/ob background. These effects possibly also contribute to the identified differences between sexes.…”

Nutritional combinatorial impact on the gut microbiota and plasma short-chain fatty acids levels in the prevention of mammary cancer in Her2/neu estrogen receptor-negative transgenic mice

“…A recent study by Acharya et al investigated the impact of estradiol treatment and obesity on the body weight, energy intake and gut microbiota of mice. They found that estradiol provided protection against HFD-induced weight gain with increased levels of the S24-7 bacterial family [ 77 ]. Lachnospiraceae family of bacteria have the ability to generate energy in the host by degradation of polysaccharides in the plants [ 78 ].…”