Options for treatment of obesity include dietary approaches and bariatric surgery. Previous studies have shown that weight loss interventions have an impact on gut microbiota. However, a pattern of ...gut microbiota changes associated with weight loss independently of the type of intervention has not been described yet. This study includes 61 individuals who followed different weight loss strategies in three different trials: 21 followed a hypocaloric Mediterranean diet (MedDiet), 18 followed a very-low-calorie ketogenic diet (VLCKD) and 22 patients underwent sleeve gastrectomy bariatric surgery (BS). Gut microbiota profile was assessed by next-generation sequencing. A common taxon that had significantly changed within the three weight loss interventions could not be find. At the family level,
significantly increased its abundance with MedDiet and VLCKD, whilst
and
significantly increased with VLCKD and BS. At genus level, in VLCKD and BS,
and
significantly increased their abundance whilst
decreased. At the species level, BS and VLCKD produced an increase in
and a decrease in
and
, whilst
increased its abundance after the BS and MedDiet. Predicted metagenome analysis suggested that most of the changes after VLCKD were focused on pathways related to biosynthesis and degradation/utilization/assimilation, while BS seems to decrease most of the biosynthesis pathways. MedDiet was enriched in several pathways related to fermentation to short-chain fatty acids. Our results show that weight loss is not associated with a specific pattern of gut microbiota changes independently of the strategy used. Indeed, gut microbiota changes according to type of weight loss intervention.
Macrophages are key effector cells in obesity-associated inflammation. G protein-coupled receptor kinase 2 (GRK2) is highly expressed in different immune cell types. Using LysM-GRK2
+/−
mice, we ...uncover that a reduction of GRK2 levels in myeloid cells prevents the development of glucose intolerance and hyperglycemia after a high fat diet (HFD) through modulation of the macrophage pro-inflammatory profile. Low levels of myeloid GRK2 confer protection against hepatic insulin resistance, steatosis and inflammation. In adipose tissue, pro-inflammatory cytokines are reduced and insulin signaling is preserved. Macrophages from LysM-GRK2
+/−
mice secrete less pro-inflammatory cytokines when stimulated with lipopolysaccharide (LPS) and their conditioned media has a reduced pathological influence in cultured adipocytes or naïve bone marrow-derived macrophages. Our data indicate that reducing GRK2 levels in myeloid cells, by attenuating pro-inflammatory features of macrophages, has a relevant impact in adipose-liver crosstalk, thus preventing high fat diet-induced metabolic alterations.
Both oxidative stress and intestinal permeability are increased in hyperglycemic situations and have been shown to be reduced by metformin in type 2 diabetes mellitus (T2DM) patients. The aim of this ...study was to elucidate the effect of metformin on oxidative stress and intestinal permeability in women with gestational diabetes mellitus (GDM) treated with metformin compared to those treated with insulin and healthy controls. A total of 120 women were included from August 2016 to February 2022: 41 received metformin (MET group), 38 received insulin (INS group), and 41 were healthy controls. Baseline and antenatal visits were carried out at 25.4 ± 4.8 and 36.1 ± 0.8 weeks of pregnancy, respectively. Advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC), and zonulin levels were measured at every visit. Zonulin levels from baseline to prepartum visit increased significantly in both healthy controls (0.6 ± 0.9 to 1.2 ± 1.7 ng/mL, p = 0.004) and the INS group (0.4 ± 0.3 to 0.6 ± 0.5 ng/mL, p = 0.034) but did not significantly change in the MET group (0.4 ± 0.4 to 0.5 ± 0.4 ng/mL, p = 0.202). However, TAC and AOPP levels significantly increased in women with GDM, both in the INS and MET groups but not in the healthy controls. In conclusion, in our population, metformin has been shown to avoid an increase in intestinal permeability but failed to avoid an increase in oxidative stress related to hyperglycemia.
Vitamin D deficiency is highly prevalent in pregnant women and has been related to a higher risk of gestational diabetes mellitus (GDM). The aim of this study is to analyze vitamin D status evolution ...in a population of pregnant women with and without GDM. Two-hundred women were included from January 2019 to February 2022 as follows: Control group -CG-, Lifestyle group -LG- (GDM not requiring insulin), and Insulin group -IG- (GDM requiring insulin). Visits were carried out at baseline, antenatal, postpartum, and 1 year after birth. Vitamin D levels, weight, and insulin resistance were measured at every visit. Data about the season, vitamin D supplementation, Mediterranean diet adherence, and physical activity were included. In the three groups, 134 women were included in the CG, 43 in the LG, and 23 in the IG. Vitamin D levels were similar among the groups at baseline, but they were significantly higher in the LG and IG in comparison with the CG at the antenatal visit and significantly higher in the IG vs. CG and LG at the postpartum and 1 year after birth visits. Vitamin D levels were independently related to vitamin D supplementation and the season at baseline, to the season and belonging to the LG or IG at the antenatal visit, and were only independently associated with belonging to the IG at postpartum and 1 year after birth visits. In conclusion, in our population, women with GDM requiring insulin had higher levels of vitamin D in comparison with those not requiring insulin and healthy controls at postpartum and 1 year after pregnancy. Requiring insulin during pregnancy seems to be a factor that independently determines the levels of vitamin D until 1 year after birth. More studies are required to reproduce these data in other populations and to elucidate the mechanisms underlying these findings.
SCOPE: The effects that fatty acids (FAs) exert on G protein‐coupled receptor‐120 (GPR120) levels, a receptor for FAs, are still unknown. We analyzed the association between GPR120 and obesity, and ...the FA effects on its expression. METHODS AND RESULTS: GPR120 levels were analyzed in visceral adipose tissue (VAT) from nonobese and morbidly obese subject. VAT GPR120 mRNA and protein levels were lower in morbidly obese subjects (p = 0.004). After, these subjects underwent a high‐fat meal. GPR120 mRNA expression in peripheral blood mononuclear cells in the fasting state was lower in morbidly obese subjects (p = 0.04), with a decrease 3 h after a high‐fat meal only in morbidly obese subjects (p = 0.043). Also, incubations of visceral adipocytes from these subjects were made with different FAs. In nonobese subjects, palmitic, oleic, linoleic, and docosahexaenoic acids produced an increase in GPR120 mRNA and protein levels (p < 0.05). In morbidly obese subjects, only linoleic acid produced an increase in GPR120 mRNA and protein levels (p < 0.05). CONCLUSION: Morbidly obese subjects had lower GPR120 mRNA and protein levels in VAT and a lower mRNA expression after a high‐fat meal in peripheral blood mononuclear cells. The FAs effect on GPR120 mRNA and protein levels in visceral adipocytes was lower in morbidly obese subjects.
Little is known about the influence of gastric microbiota on host metabolism, even though the stomach plays an important role in the production of hormones involved in body weight regulation and ...glucose homeostasis. Proton pump inhibitors (PPIs) and Helicobacter pylori alter gut microbiota, but their impact on gastric microbiota in patients with obesity and the influence of these factors on the metabolic response to bariatric surgery is not fully understood. Forty-one subjects with morbid obesity who underwent sleeve gastrectomy were included in this study. The H. pylori group was established by the detection of H. pylori using a sequencing-based method (
= 16). Individuals in whom H. pylori was not detected were classified according to PPI treatment. Gastric biopsy specimens were obtained during surgery and were analyzed by a high-throughput-sequencing method. Patients were evaluated at baseline and 3, 6, and 12 months after surgery. β-Diversity measures were able to cluster patients according to their gastric mucosa-associated microbiota composition. H. pylori and PPI treatment are presented as two important factors for gastric mucosa-associated microbiota. H. pylori reduced diversity, while PPIs altered β-diversity. Both factors induced changes in the gastric mucosa-associated microbiota composition and its predicted functions. PPI users showed lower percentages of change in the body mass index (BMI) in the short term after surgery, while the H. pylori group showed higher glucose levels and lower percentages of reduction in body weight/BMI 1 year after surgery. PPIs and H. pylori colonization could modify the gastric mucosa-associated microbiota, altering its diversity, composition, and predicted functionality. These factors may have a role in the metabolic evolution of patients undergoing bariatric surgery.
The gut microbiota has been shown to have an impact on host metabolism. In the stomach, factors like proton pump inhibitor treatment and Helicobacter pylori haven been suggested to alter gut microbiota; however, the influence of these factors on the metabolic response to bariatric surgery has not been fully studied. In this study, we highlight the impact of these factors on the gastric microbiota composition. Moreover, proton pump inhibitor treatment and the presence of Helicobacter pylori could have an influence on bariatric surgery outcomes, mainly on body weight loss and glucose homeostasis. Deciphering the relationship between gastric hormones and gastric microbiota and their contributions to bariatric surgery outcomes paves the way to develop gut manipulation strategies to improve the metabolic success of bariatric surgery.
Background: The effects of different types of fatty acids on the gene expression of key players in the IRS1/PI3K signaling pathway have been poorly studied. Material and Methods: We analyzed IRS1, ...p85α, and p110β mRNA expression and the fatty acid composition of phospholipids in visceral adipose tissue from patients with morbid obesity and from non-obese patients. Moreover, we analyzed the expression of those genes in visceral adipocytes incubated with oleic, linoleic, palmitic and dosahexaenoic acids. Results: We found a reduced IRS1 expression in patients with morbid obesity, independent of insulin resistance, and a reduced p110β expression in those with lower insulin resistance. A positive correlation was found between p85α and stearic acid, and between IRS1 and p110β with palmitic and dosahexaenoic acid. In contrast, a negative correlation was found between p85α and oleic acid, and between IRS1 and p110β with linoleic, arachidonic and adrenic acid. Incubation with palmitic acid decreased IRS1 expression. p85α was down-regulated after incubation with oleic and dosahexaenoic acid and up-regulated with palmitic acid. p110β expression was increased and decreased after incubation with oleic and palmitic acid, respectively. The ratio p85α/p110β was decreased by oleic and dosahexaenoic acid and increased by palmitic acid. Conclusions: Our in vitro results suggest a detrimental role of palmitic acid on the expression of gene related to insulin signaling pathway, with oleic acid being the one with the higher and more beneficial effects. DHA had a slight beneficial effect. Fatty acid-induced regulation of genes related to the IRS1/PI3K pathway may be a novel mechanism by which fatty acids regulate insulin sensitivity in visceral adipocytes.
Incidental prophylactic surgeries are performed in certain situations. Incidental prophylactic appendectomies were common practice within opened bariatric surgeries. The gut microbiota has emerged as ...an important actor within the homeostasis of the host. A new hypothesis has been formulated about the appendix function in relation to gut microbiota. Our objective was to study the gut microbiota profiles of patients that had suffered from an incidental prophylactic appendectomy during their bariatric surgeries, while comparing them to patients whose appendixes had remained intact. A case-control observational prospective study of 40 patients who underwent bariatric surgery, with or without an incidental prophylactic appendectomy, during 2004-2008 with an evaluation of their gut microbiota populations at the end of 2016 was conducted by sequencing the 16 S rRNA gene by Next Generation Sequencing of patients' stools and appendix tissues. Patients with their appendix removed showed lower levels of richness and diversity of their gut microbiota populations.
,
,
, and
levels were increased in the Intact group, while
suffered an expansion in the group without the appendix. Moreover, a linear regression
introduced the concept that
and
may be implicated in insulin regulation. Thus, gut microbiota should be considered in the decisions of practical surgery, regarding the appendix as a mediator of homeostasis in the host.
and
require further investigation as key bacteria implicated in insulin regulation.
To analyze the effect of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence and obstetrical and perinatal outcomes, in ...comparison to usual diagnostic approaches.
Data from women referred to GDM diagnosis from 1 September to 30 November 2019 were retrospectively collected (2019-group). The same data from the same period in 2020 were prospectively collected (2020-group). In both cases, a two-step diagnostic approach was used, the first step being a screening test (1 h 50 goral glucose tolerance test, OGTT). In 2019 it was followed by a 100 gr OGTT for diagnosis. In 2020, this was replaced by a blood test for the measurement of plasma glucose and HbA1c, according to alternative GDM diagnostic criteria during the COVID-19 pandemic.
From 237 women in the 2019 group, 40 (16.9%) were diagnosed with GDM, while from 255 women in the 2020 group, 37 (14.5%) had GDM (
= 0.470). More women in the 2020 group, in comparison to the 2019 group, were nulligravid (41.9% vs. 47.2%,
= 0.013), had a personal history of GDM (11.4% vs. 4.6%,
= 0.013) and had macrosomia in previous pregnancies (10.2% vs. 2.1%,
= 0.001). Obstetrical and perinatal outcomes were similar when comparing women with GDM to non-GDM women in the 2019 and 2020 groups and between GDM women and non-GDM women.
In a Spanish population, GDM prevalence during the COVID-19 pandemic using the alternative diagnostic criteria was similar to that found in 2019 using the usual diagnostic criteria. Despite women referred for GDM diagnosis during the pandemic having more GDM risk factors, obstetrical and perinatal outcomes were comparable to those observed before the pandemic.
Summary Background & aims To investigate the relationship between levels of 25-hydroxyvitamin D and the incidence of type 2 diabetes in a Spanish population. Methods We undertook a population-based ...prospective study in a population from southern Spain. The first phase of the study (1996–1998) included 1226 individuals. Of this original cohort, 988 persons were reassessed in 2002–2004 and 961 in 2005–2007. Measurements were made of 25-hydroxyvitamin D and intact parathyroid hormone in 2002–2004 and an oral glucose tolerance test was done in three time points. Results The incidence of diabetes in subjects with 25-hydroxyvitamin D levels ≤18.5 ng/mL (percentile 25) was 12.4% vs 4.7% in subjects with levels >18.5 ng/mL. The likelihood of having diabetes during the four years of follow-up was significantly lower in the subjects with higher levels of 25-hydroxyvitamin D OR = 0.17 (0.05–0.61). None of the subjects with levels higher than 30 ng/mL developed diabetes. Conclusion In this prospective study, we found a significant inverse association between serum 25-hydroxyvitamin D levels and the risk for type 2 diabetes in a population from the south of Spain.
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