Lower Insulin Levels Research Articles

Improvements in Insulin Resistance and Glucose Metabolism Related to Breastfeeding Are Not Mediated by Subclinical Inflammation

Background: Lactation is known to improve insulin resistance, but this phenomenon remains poorly understood. Our goal was to evaluate whether subclinical inflammation could mediate the association between breastfeeding (BF) and improvement in glucose metabolism and markers of insulin resistance (MIRs) in the postpartum. Methods: A total of 95 adult women (≥18 years) with a BMI ≥ 25 kg/m2 from the outpatient clinic of the Federal University of São Paulo were followed from early pregnancy until 60 to 180 days postpartum. The patients were divided based on their BF status: BF and non-BF groups. A latent variable termed SubInf was created incorporating inflammation-related biomarkers: adiponectin, E-selectin, branched-chain amino acids, zonulin, copeptin, and lipopolysaccharides. The association of BR with MIRs in the postpartum was evaluated through linear regression analysis, and mediation analysis was performed to evaluate the role of SubInf in this association. Results: The groups were similar regarding gestational diabetes mellitus (GDM) prevalence, pre-gestational BMI, caloric intake, physical activity, and postpartum weight loss. The BF group presented lower levels of triglycerides (TGs), fasting glucose, fasting insulin, TG/HDLcholesterol ratio (TG/HDL), TyG index, and HOMA-IR compared to the non-BF group. A linear regression analysis adjusted for scholarity, parity, pre-gestational BMI, GDM, weight gain during pregnancy, and mode of delivery revealed an inverse association between BF and fasting glucose [−6.30 (−10.71 to −1.89), p = 0.005), HOMA-IR [−0.28 (−0.50 to −0.05), p = 0.017], TyG index [−0.04 (−0.06 to −0.01), p = 0.002], and TG/HDL ratio [−0.23 (−0.46 to −0.01), p = 0.001]. In the mediation analysis, SubInf did not mediate the indirect effect of BF on MIRs. Conclusions: In overweight and obese women, an association between BF and improvement in MIRs in the postpartum was seen, corroborating that BF should be stimulated, especially in these cardiometabolic high-risk women. Subclinical inflammation did not seem to mediate this association.

Network pharmacology and transcriptomics explore the therapeutic effects of Ermiao Wan categorized formulas for diabetes in mice

Ermiao wan (EMW) is a classical traditional Chinese medicine formula, with two modified versions including Sanmiao wan (SMW) and Simiao wan (FMW). These Ermiao wan categorized formulas (ECFs) are traditionally used to treat gouty arthritis and hyperuricemia. However, their potential benefits and mechanisms on diabetes remain to be explored. This study aims to investigate the overall effects and biological differences of ECFs in high fat diet (HFD)-fed mice based on network pharmacology and transcriptomics. ECFs significantly reduced body weight, improved oral glucose tolerance, decreased fat accumulation, and lowered serum insulin and inflammatory cytokine levels in HFD-fed mice. FMW had better efficacy than EMW and SMW. Network pharmacology analysis revealed that ECFs targeted functional modules associated with chronic inflammation, lipid metabolism, and glucose metabolism. Transcriptome results also showed ECFs could inhibit genes associated with inflammation and upregulated some genes in lipid metabolism. Comprehensive analysis and QPCR verification indicated the beneficial effects of ECFs on diabetes might be attributed to the regulation of Ddit3, Ccl2, Esr1, and Cyp7a1. This study provides a theoretical basis for the clinical use of ECFs.

Endocrine pathology in young rabbits with cystic fibrosis

BackgroundCystic fibrosis (CF) is an autosomal recessive genetic disorder caused by loss-of-function mutations in the CF transmembrane conductance regulator gene. CF-related pancreatic lesions are known to cause exocrine dysfunctions such...

The Induction of Diabetes by High-Sugar and High-Fat Diets and Potential Applications of Healthy Eating

The rising prevalence of diabetes has intensified research in this field. Among the various causes of diabetes, insulin resistance plays a crucial role. High-sugar, high-fat diets are known to induce hyperglycemia and obesity, which significantly affect the progression of insulin resistance. It should be noted that obesity can significantly increase insulin resistance, thereby inducing prediabetes and aggravating diabetic symptoms. Additionally, such diets disturb the balance of intestinal flora. Controlling carbohydrate intake through low-carb or ketogenic diets can effectively improve glucose and lipid metabolism, improving insulin sensitivity, reducing insulin resistance, and lowering insulin levels. Adjustments to diet can also help shape a healthy gut flora composition. Furthermore, consuming natural products like flavonoids can also contribute to the improvement of diabetic symptoms. This article summarizes the impact of high-sugar, high-fat diets on the progression of diabetes, their effects on insulin resistance and intestinal flora, and the regulatory benefits of a healthy diet in managing diabetes.

Exploring diet as a source of plasticizers in pregnancy and implications for maternal second-trimester metabolic health

Background and objectivesDiet plays critical roles in modulating maternal metabolic health in pregnancy, but is also a source of metabolic-disrupting phthalates and their replacements. We aimed to evaluate whether the effects of better diet quality on favorable maternal metabolic outcomes could be partially explained by lower exposure to phthalates/replacements. MethodsAt 13 weeks gestation, 295 Illinois women (enrolled 2015–2018) completed a three-month food frequency questionnaire that we used to calculate the Alternative Healthy Eating Index (AHEI)-2010 to assess diet quality. We quantified 19 metabolites, reflecting exposure to 10 phthalates/replacements, in a pool of five first-morning urine samples collected monthly across pregnancy. We measured 15 metabolic biomarkers in fasting plasma samples collected at 17 weeks gestation, which we reduced to five uncorrelated principal components (PCs), representing adiposity, lipids, cholesterol, inflammation, and growth. We used linear regression to estimate associations of diet quality with [1] phthalates/replacements and [2] metabolic PCs, as well as [3] associations of phthalates/replacements with metabolic PCs. We estimated the proportion of associations between diet quality and metabolic outcomes explained by phthalates/replacements using a causal mediation framework. ResultsOverall, every 10-point improvement in AHEI-2010 score was associated with −0.15 (95% CI: −0.27, −0.04) lower adiposity scores, reflecting lower glucose, insulin, C-peptide, leptin, C-reactive protein, but higher adiponectin biomarker levels. Every 10-point increase in diet quality was also associated with 18% (95%CI: 7%, 28%) lower sum of di-2-ethylhexyl terephthalate urinary metabolites (∑DEHTP). Correspondingly, each 18% increase in ∑DEHTP was associated with 0.03 point (95% CI: 0.01, 0.05) higher adiposity PC scores. In mediation analyses, 21% of the inverse relationship between diet quality and adiposity PC scores was explained by lower ∑DEHTP. ConclusionsThe favorable impact of diet quality on maternal adiposity biomarkers may be partially attributed to lower metabolite concentrations of DEHTP, a plasticizer allowed to be used in food packaging materials.

Effects of a Carbohydrate Meal on Lipolysis

Background: Due to the increasing prevalence of obesity and type 2 diabetes, effective dietary recommendations are needed. Previously, we developed the low-insulin method: by avoiding insulinogenic, i.e., insulin-release-triggering foods, insulin secretion becomes reduced, lipolysis is stimulated, and energy production is shifted to ketosis with excess ketone bodies exhaled in the form of acetone. Now, we investigate how quickly stable ketosis (defined as fasting breath acetone concentration ≥ 7.0 ppm) is achieved, whether and for how long a carbohydrate meal inhibits ketosis, and whether the responses differ in healthy adults with different insulin levels. Methods: An oral glucose tolerance test was conducted, and body composition and fasting insulin were determined at the beginning and end of the 14-day study. Participants (n = 10) followed a ketogenic diet and performed continuous glucose monitoring. Ketosis levels were determined by measuring breath acetone concentrations. On day 8, two white bread rolls with jam (72 g carbohydrates) were consumed for breakfast. Results: After seven days, all participants achieved stable ketosis (defined as fasting breath acetone concentration ≥ 7.0 ppm), which dropped from 8.2 to 5.7 ppm (p = 0.0014) after the carbohydrate meal. It took five days to achieve stable ketosis again. The stratification of participants into tertiles according to their fasting insulin levels demonstrated that individuals with low fasting insulin levels achieved stable ketosis again after two days and those with medium insulin levels after five days, while those with high baseline values did not reach stable ketosis by the end of the study. Conclusions: By carbohydrate restriction, stable ketosis can be achieved within one week. However, a single carbohydrate meal inhibits ketosis for several days. This effect is pronounced in individuals with elevated fasting insulin levels.

Medium-chain fatty acid receptor GPR84 deficiency leads to metabolic homeostasis dysfunction in mice fed high-fat diet.

Overconsumption of food, especially dietary fat, leads to metabolic disorders such as obesity and type 2 diabetes. Long-chain fatty acids, such as palmitoleate are recognized as the risk factors for these disorders owing to their high-energy content and lipotoxicity. In contrast, medium-chain fatty acids (MCFAs) metabolic benefits; however, their underlying molecular mechanisms remain unclear. GPR84 is an MCFA receptor, particularly for C10:0. Although evidence from invitro experiments and oral administration of C10:0 in mice suggests that GPR84 is related to the metabolic benefits of MCFAs via glucose metabolism, its precise roles invivo remain unclear. Therefore, the present study investigated whether GPR84 affects glucose metabolism and metabolic function using Gpr84-deficient mice. Although Gpr84-deficient mice were lean and had increased endogenous MCFAs under high-fat diet feeding conditions, they exhibited hyperglycemia and hyperlipidemia along with lower plasma insulin and glucagon-like peptide-1 (GLP-1) levels compared with wild-type mice. Medium-chain triglyceride (C10:0) intake suppressed obesity, and improved plasma glucose and lipid levels, and increased plasma GLP-1 levels in wild-type mice; however, these effects were partially attenuated in Gpr84-deficient mice. Our results indicate that long-term MCFA-mediated GPR84 activation improves the dysfunction of glucose and lipid homeostasis. Our findings may be instrumental for future studies on drug development with GPR84 as a potential target, thereby offering new avenues for the treatment of metabolic disorders like obesity and type 2 diabetes.

Maternal Broccoli Powder Intake Ameliorates Insulin Resistance and Inflammation via AMPK/mTOR Pathway in the Livers of High-Fructose-Fed Male Rat Offspring Exposed to Maternal Protein Restriction.

Sub-optimal prenatal conditions such as maternal undernutrition during pregnancy and lactation posit high risks of adult metabolic diseases. High fructose intake causes insulin resistance and liver inflammation contributing to metabolic diseases. However, food-based preventive measure for these metabolic diseases in the offspring is under-researched. This study aims to investigate the effect of maternal broccoli powder (BP) intake during lactation on insulin resistance and liver inflammation in high-fructose-diet-fed adult male offspring exposed to maternal protein restriction. Pregnant Wistar rats are provided normal protein (NP) or low protein (LP) diets and 0% or 0.74% BP-containing NP diets and 0% or 0.74% BP-containing LP diet during lactation. At weaning, offspring receiving water (W) or 10% fructose solution (Fr) are assigned into six groups: NP/NP/W, NP/NP/Fr, NP/NPBP/Fr, LP/LP/W, LP/LP/Fr, and LP/LPBP/Fr. At week 13, plasma insulin, macrophage infiltration, activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) phosphorylation, and autophagy flux markers are examined. LP/LPBP/Fr shows lower insulin levels and Homeostatic model assessment for insulin resistance (HOMA-IR) values than LP/LP/Fr. Liver macrophage infiltration are decreased in LP/LPBP/Fr. LP/LPBP/Fr exhibits upregulated AMPK phosphorylation, downregulated mTOR phosphorylation, and increased Microtubule-associated protein1A/1B-light chain 3B-II (LC3B-II) levels. Maternal BP intake during lactation ameliorates insulin resistance and inflammation in the livers of adult offspring on a high-fructose diet from LP mothers.

Nutritional aspects in neuroendocrine neoplasms. bridging the gap between dietary interventions and cancer care strategies: a scoping review.

Neuroendocrine neoplasms (NENs) represent heterogeneous tumors arising from neuroendocrine cells in different organs. Despite growing interest in the nutritional aspects of NEN management, research in this area is limited. Aim of this review is to summarize the current state of knowledge, highlight research gaps, and underscore the significance of nutrition in the comprehensive care of NEN patients. We conducted an extensive bibliographic search focusing on studies (including retrospective and prospective studies, systematic reviews, case series, and guidelines) exploring the relationship between nutritional assessments, dietary interventions, micronutrient deficiencies, and their impact on NEN outcomes. Significant gaps exist in current research, particularly in understanding the specific nutritional needs of NEN patients and how tailored nutritional interventions can improve clinical outcomes. Evidence suggests that a high-fat Western diet may promote the growth of NEN, while a Mediterranean diet may help lower insulin levels and strengthen the immune system, potentially preventing tumor development. The ketogenic diet and intermittent fasting may also have positive impacts. Addressing common micronutrient deficiencies, such as vitamin D and niacin, is crucial to mitigate disease progression. There's a crucial need for future studies to include a comprehensive nutritional assessment incorporating patient-reported outcomes, to fully capture the impact of nutritional strategies. Nutritional management, an important but under-researched facet of NEN treatment, significantly improves patients' quality of life and survival. Integrating nutrition into personalized cancer care is essential, highlighting the role of nutritional strategies in optimizing patient outcomes.

7260 Nuclear Corepressor 1 (NCoR1) plays important role in the regulation of insulin gene transcription in mouse Min6 pancreatic beta cells

Abstract Disclosure: H. Shimizu: None. Y. Horibata: None. I. Amano: None. M.J. Ritter: None. M. Ohyama: None. M. Domae: None. H. Sugimoto: None. A.N. Hollenberg: None. Background: Nuclear Corepressor 1 (NCoR1) is a transcriptional corepressor which has been recognized as an important player in the regulation of hepatic lipogenesis and hematopoiesis in mouse embryo. NCoR1 is also widely expressed in mouse insulin sensitive organs, for instance adipocyte, skeletal muscle, and hepatocytes. Mouse genetic deletion strategies of either NCoR1 or SMRT(NCoR2; an ortholog corepressor of NCoR1) demonstrated that each corepressor effects the insulin sensitivity in the tissues. However, the role of each corepressor in pancreatic beta cell is not still elucidated. Methods: To clarify this, we took the gene-targeting strategy for NCoR1 using CRISPR Cas-9 and made the pancreatic beta Min6 clone which lacks NCoR1 protein (Min6-NCoR1KO; NKO cells). For this study, wild type Min6 cells (WT) and NKO cells were cultured in the Dulbecco's DMEM medium with 10% fetal bovine serum for 4-5 days, and the expression analyses compared between two cell types were performed. Results: Both comprehensive proteomics and following expression analyses compared between WT and NKO cells demonstrated that NKO cells have significantly lower expression level of insulin (INS-1 and INS-2), accompanied with high expression of histone deacetylase 6 (HDAC6). For further analyses, we also made the Min6 clone which lacks SMRT(Min6-SMRTKO; SKO cells). Interestingly, SKO cell had higher insulin and lower HDAC6 levels, accompanied with significant up-regulation of NCoR1. Conclusion: Taken together, these data indicate that NCoR1 has dominant effects in the regulation of both histone deacetylation and insulin gene transcription in Min6 cells. Further investigations for the function of NCoR1 in the insulin gene transcription observed in Min6 cells will be needed. Presentation: 6/2/2024

6712 Intractable Hypoglycemia: A Clue to Tumor Diagnosis

Abstract Disclosure: N. Kharkongor Chengappa: None. E.I. Krug: None. Background: Non-Islet Cell Tumor Hypoglycemia (NICTH) known as Doege-Potter syndrome, is a rare paraneoplastic syndrome of hypo-insulinemic hypoglycemia caused by excessive production of partially processed IGF-II from a solitary fibrous tumor (SFT).We present a case of a patient admitted with intractable hypoglycemia leading to the diagnosis and treatment of a large pelvic SFT. Clinical Case: A 59-year-old male with type 2 Diabetes Mellitus on metformin mono therapy, was admitted after he collapsed at work and was found to have blood glucose (BG) of 22 mg/dl. He was previously in his usual state of health except for an increase in his shoe size over the past year. Physical examination revealed coarse thick skin, large coarse bullous nose, enlarged fingers and a non-tender, firm abdomen with no obvious organomegaly. Laboratory results including CBC, CMP and thyroid function were normal. ACTH stimulation test revealed normal adrenal function. Hypoglycemic drug screen and insulin antibodies were negative. During a hypoglycemic event (BG of 45mg/dl) he had C-peptide level < 0.1ng/ml, beta-hydroxybutyrate levels of <0.05 and insulin level <0.4uIU/ml, indicating non-insulin mediated hypoglycemia. IGF-I and IGF-II levels were ordered. Due to a concern for paraneoplastic etiology of hypoglycemia. CT scan revealed a 20 cm solid mass, filling most of the pelvis and extending into the lower abdomen. Further investigations revealed normal PSA, CEA, CA19-9 and undetectable hCG and AFP levels. MRI confirmed a presence of 23 cm pelvic mass with few areas of central necrosis, extending into the lower abdomen. CT-guided biopsy revealed spindle cell neoplasm consistent with SFT. The patient underwent pelvic mass resection. Postoperatively, hypoglycemia resolved with BG readings of 138mg/dl to 178mg/dl. Surgical pathology results confirmed malignant SFT with positive STAT 6 and CD34 markers. IGF-II level obtained prior to surgery was markedly elevated at 2029 ng/ml (38-267 ng/mL). Conclusion: NICTH was described in 1930 by KW Doege and RP Potter. Less than 5% of patients with SFTs develop NICTH. Diagnosis requires manifestation of Whipple's triad, low insulin, pro-insulin and C-peptide levels, elevated IGF-II levels, or an IGF-I/IGF-II ratio>2, and the identification of the tumor. Positive immunohistochemical stain of the tumor for STAT6 confirms the diagnosis. Management involves resection of the tumor when feasible or debulking. For higher-risk tumors, radiation therapy may be considered. In inoperable cases, glucocorticoids, recombinant hGH and glucagon are recommended for palliation of hypoglycemia. Octreotide and Diazoxide are ineffective in NICTH.

Determination of beneficial effects of cuminaldehyde on hyperglycemiaassociated kidney malfunctions.

Type 1 diabetes mellitus is defined by the autoimmune destruction of pancreatic β cells, with diabetic nephropathy being a significant consequence. Recently, cuminaldehyde has been shown protective ability against various pathophysiology. However, its nephroprotective and anti-diabetic potential has not yet been fully understood. We, therefore, conducted the present study to evaluate the anti-hyperglycemic potential of cuminaldehyde in NRK52E cells without (control) or with high glucose medium to emulate hyperglycemic conditions. Cuminaldehyde pre-treatment at an optimal concentration of 175μM prior to high glucose addition restricted excessive reactive oxygen species (ROS) production and maintained cellular morphology to almost normal. The inhibitor study using N-acetyl-l-cysteine confirmed that blocking of ROS assists NRK52E cells in evading apoptosis. In addition, hyperglycemia was induced in 6-week-old Swiss albino mice in this investigation through the intraperitoneal injection of streptozotocin (150mgkg-1 body weight). Hyperglycemia increased the kidney-to-body weight ratio, lowered serum insulin levels, and led to significant renal tissue damage compared to control mice. Moreover, hyperglycemia disturbs cellular redox equilibrium by decreasing antioxidant enzyme functions and promoting inflammatory cytokines in kidney tissue. Administering cuminaldehyde at a dosage of 10mgkg-1 body weight for 5weeks daily after the onset of diabetes effectively ameliorated the aforementioned anomalies and reversed kidney damage by regulating inflammation-induced cell death. Overall, the research demonstrated that cuminaldehyde has hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties. We believe that after conducting extensive research, this unique molecule can be used in clinical trials against diabetic nephropathy in future.

Comparison of the effects of losartan potassium and benazepril in the treatment of hypertensive patients with insulin resistance.

To compare the efficacy of losartan potassium (LP) and benazepril in the treatment of hypertensive patients with insulin resistance (IR). This is a retrospective analysis of the clinical data of 155 hypertensive patients with IR admitted to Shanghai Pudong New Area People's Hospital from March 2021 to March 2023. Of these 76 received LP treatment (LP group), and 79 received benazepril treatment (benazepril group). Blood pressure levels, blood glucose and insulin levels, treatment efficacy, and incidence of adverse reactions before and after the treatment in both groups were compared. After the treatment, diastolic and systolic blood pressure in the two groups significantly decreased compared to pre-treatment levels (P<0.05), with no significant difference between the two groups (P>0.05). After the treatment, levels of fasting plasma glucose (FPG), 2-hours plasma glucose (2hPG), fasting insulin (FINS), 2-hours insulin (2hINS), and insulin sensitivity index (ISI) in both groups significantly decreased compared to pre-treatment levels (P<0.05), with no significant difference between the two groups (P>0.05). There was no significant difference in the total efficacy and the incidence of adverse reactions between the two groups (P>0.05). The efficacy of LP and benazepril in treating hypertension with IR is equivalent. Both are safe and can effectively lower blood sugar and insulin levels, alleviate IR, and lower blood pressure.

Exploring Factors Influencing Stroke Risk: Insights From a Predictive Analysis.

Introduction Stroke is a serious medical condition characterized by the sudden interruption of blood flow to the brain, resulting in the death of brain cells. It is a leading cause of long-term disability and mortality worldwide. Stroke has some associated risk factors, both modifiable and non-modifiable ones.As for non-modifiable risk factors, these are age, gender (men are more vulnerable), and family history of stroke.The controllable or adjustable risk factors include hypertension (high blood pressure), diabetes, smoking, high cholesterol levels, obesity, and insulin resistance. Methods In our study, we collected data from 229 patients which were originally collected for clinical purposes and were retrospectively analyzed. These data contain features such assex and age, the presence of ischemic heart disease (IHD) or stroke history, and different blood sugar readings. These measurements include fasting blood sugar (FBS), postprandial blood sugar (PPBS), HbA1c%, and insulin levels (fasting and postprandial).Furthermore, cholesterol was also tested, such as total cholesterol, triglycerides (TGL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL). Surprisingly, stroke was observed in 24of the 205 patients. This contrast permits us to be concerned with the chance of the association between stroke and insulin levels. Given the imbalanced nature of our outcome variable (stroke occurrence), the primary analytical method will be logistic regression. Results In this cross-sectional study, we investigated the association between high insulin levels (both fasting and postprandial) and the occurrence of stroke within a dataset of 229 patients. Out of the 229 included cases, 102 individuals were female (44.5%) and 127 individuals were male (55.5%). Twenty-four cases have ischemic heart disease (10.5%). Among the analyzed cases, 24 individuals have a history of stroke. The average age of the sample is approximately 57 years ± 14.87. There was no significant difference between the males and females in most of the descriptive statistics. However, females experienced significantly higher levels of postprandial glucose level and significantly lower levels of postprandial insulin. According to our predictive model, we found that an increase in fasting insulin levels was linked to a lower risk of stroke occurrence. On the other hand, increasing insulin postprandial levels and age were associated with an increased risk of stroke. Conclusion Our study identified age, fasting insulin, and postprandial insulin as key factors influencing stroke risk. Higher fasting insulin levels were associated with reduced risk, while increased postprandial insulin and age were linked to higher risk. Blood glucose, cholesterol, and triglycerides had minor effects. Notably, higher total cholesterol and triglyceride levels were slightly associated with lower stroke occurrence. Further research with larger samples is needed for validation.

Association between thermogenic brown fat and genes under positive natural selection in circumpolar populations

BackgroundAdaptation to cold was essential for human migration across Eurasia. Non-shivering thermogenesis through brown adipose tissue (BAT) participates in cold adaptation because some genes involved in the differentiation and function of BAT exhibit signatures of positive natural selection in populations at high latitudes. Whether these genes are associated with the inter-individual variability in BAT thermogenesis remains unclear. In this study, we evaluated the potential associations between BAT activity and single nucleotide polymorphisms (SNPs) in candidate gene regions in East Asian populations.MethodsBAT activity induced by mild cold exposure was measured in 399 healthy Japanese men and women using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). The capacity for cold-induced thermogenesis and fat oxidation was measured in 56 men. Association analyses with physiological traits were performed for 11 SNPs at six loci (LEPR, ANGPTL8, PLA2G2A, PLIN1, TBX15-WARS2, and FADS1) reported to be under positive natural selection. Associations found in the FDG-PET/CT population were further validated in 84 healthy East Asian men and women, in whom BAT activity was measured using infrared thermography. Associations between the SNP genotypes and BAT activity or other related traits were tested using multiple logistic and linear regression models.ResultsOf the 11 putative adaptive alleles of the six genes, two intronic SNPs in LEPR (rs1022981 and rs12405556) tended to be associated with higher BAT activity. However, these did not survive multiple test comparisons. Associations with lower body fat percentage, plasma triglyceride, insulin, and HOMA-IR levels were observed in the FDG-PET/CT population (P < 0.05). Other loci, including TBX15-WARS2, which is speculated to mediate cold adaptation in Greenland Inuits, did not show significant differences in BAT thermogenesis.ConclusionsOur results suggest a marginal but significant association between LEPR SNPs. However, robust supporting evidence was not established for the involvement of other loci under positive natural selection in cold adaptation through BAT thermogenesis in East Asian adults. Given the pleiotropic function of these genes, factors other than cold adaptation through BAT thermogenesis, such as diet adaptation, may contribute to positive natural selection at these loci.

S100A8/A9-activated IFNγ+ NK cells trigger β-cell necroptosis in hepatitis B virus-associated liver cirrhosis

Background and aimsHepatitis B virus (HBV)-associated liver cirrhosis (LC), a common condition with high incidence and mortality rates, is often associated with diabetes mellitus (DM). However, the molecular mechanisms underlying impaired glucose regulation during HBV-associated LC remain unclear.MethodsData from 63 patients with LC and 62 patients with LC-associated DM were analysed. Co-culture of NK cells and islet β cell lines were used to study the glucose regulation mechanism. A mouse model of LC was used to verify the effect of S100A8/A9 on the glucose regulation.ResultsHigher levels of interferon (IFN)-γ derived from natural killer (NK) cells and lower levels of insulin emerged in the peripheral blood of patients with both LC and DM compared with those from patients with LC only. IFN-γ derived from NK cells facilitated β cell necroptosis and impaired insulin production. Furthermore, S100A8/A9 elevation in patients with both LC and DM was found to upregulate IFN-γ production in NK cells. Consistently, in the mouse model for LC, mice treated with carbon tetrachloride (CCL4) and S100A8/A9 exhibited increased blood glucose, impaired insulin production, increased IFN-γ, and increased β cells necroptosis compared with those treated with CCL4. Mechanistically, S100A8/A9 activated the p38 MAPK pathway to increase IFN-γ production in NK cells. These effects were diminished after blocking RAGE.ConclusionTogether, the data indicate that IFN-γ produced by NK cells induces β cell necroptosis via the S100A8/A9–RAGE–p38 MAPK axis in patients with LC and DM. Reduced levels of S100A8/A9, NK cells, and IFN-γ could be valuable for the treatment of LC with DM. Accumulation of S100A8/A9 in patients with LC may indicate the emergence of DM.

The injection of maternal B complex vitamin during the transition period: The impact on performance, thyroid hormones levels and immunological parameters in the Sannen goats and their kids, as well as the faeces status of newborn kids.

It is proven that B vitamins through promote a wide range of metabolic pathways in animals as cofactors improve animal performance. This study was conducted to investigate the impacts of maternal B complex vitamin injection on performance and plasma parameters in goats and their offspring, as well as the faeces status of newborn kids. In this research, the pregnant goats (3 years old) were randomly divided into two groups: the control group (without B complex vitamin injection) and the B complex vitamin group (5mL B complex vitamin injection per animal). The animals were injected with 5mL B complex vitamin twice during the transition period (5 weeks pre- and 5 weeks post-kidding). The goats during the transition period and kids on days 10, 20 and 30 were weighed. Feed intake by goats and consumption of milk and starter in kids were recorded daily. The dry matter digestibility by kids was tested by collecting samples of faeces and feed for 5 days in the last week. Chemical analysis was determined using the AOAC method. The kids' faeces were prepared daily during the study. The blood samples of goats and newborn kids were taken 7 days after kidding. Then, levels of B group vitamin, as well as concentrations of liver enzymes, thyroid hormones and immunological parameters, were determined in plasma of goat and their offspring. In addition, concentrations of glucose and insulin were measured in goat plasma (Asadi et al., 2024). According to results, the performances of goats and their offspring, as well as kids' faeces status, were improved by maternal B complex vitamin injection (p<0.0001). The levels of cobalamin, pyridoxine, thiamine, folic acid, nicotinic, pantothenic and unconjugated pteridine increased in the plasma of goats and their kids in the B complex vitamin group compared with the control group during the transition period (p<0.0001). Injection of maternal B complex vitamin raised the plasma levels of triiodothyronine and tetraiodothyronine, immunoglobulin G and immunoglobulin M in goats and their offspring (p<0.0001). Higher levels of glucose and lower levels of insulin were determined in the goats injected with B complex vitamin (p<0.0001). These results suggest that maternal B complex vitamin injection is required for the improvement of performance, health status and the blood plasma parameters in pregnant goats and their kids.

Effects of Age and Diet on Triglyceride Metabolism in Mice.

Both age and diet can contribute to alterations in triglyceride metabolism and subsequent metabolic disease. In humans, plasma triglyceride levels increase with age. Diets high in saturated fats can increase triglyceride levels while diets high in omega-3 fatty acids decrease triglyceride levels. Here we asked how age and long-term diet effected triglyceride metabolism in mice. We fed male and female mice a low-fat diet, a western diet, or a diet high in polyunsaturated and omega-3 (n-3) fatty acids for up to 2 years. We measured survival, body composition, plasma triglyceride levels, chylomicron clearance, and oral fat, glucose, and insulin tolerance. Triglyceride levels in mice did not increase with age, regardless of diet. Oral fat tolerance increased with age, while chylomicron clearance remained unchanged. Mice fed western diet had decreased survival. Interestingly, mice fed the n-3 diet gained more lean mass, and had lower insulin levels than mice fed either low-fat or western diet. Moreover, triglyceride uptake into the hearts of mice fed the n-3 diet was strikingly higher than in other groups. In mice, age-induced changes in triglyceride metabolism did not match those in humans. Our data suggested that mice, like humans, had decreased fat absorption with age, but plasma triglyceride clearance did not decrease with age in mice, resulting in lower plasma triglyceride levels and improved oral fat tolerance with age. A chronic diet high in n-3 fatty acids increased insulin sensitivity and uptake of triglycerides specifically into the heart but how these observations are connected is unclear. The changes in triglyceride metabolism that occur with age in humans are not reflected in a mouse model, thus mice are likely not an ideal model for understanding how age impacts lipid metabolism and subsequent metabolic disease.A fish-oil based high-fat diet high in omega-3 fatty acids significantly increases fatty acid uptake in the heart while at the same time decreases fasting insulin levels.In future studies it will be important to understand how the omega-3 fatty acid induced increase in fatty acid uptake affects cardiac function and how it is related to other phenotypes induced by omega-3 fatty acids.

O-286 Weight loss interventions prior to infertility treatment does it make sense?

Abstract Obesity in women is negatively associated with reproductive outcomes such as decreased natural conception and pregnancy rate in assisted reproductive technique (ART), as well as increased risks of miscarriage and maternal and foetal complications, including risks of perinatal and neonatal death. The reproductive consequences of obesity stem from a combination of ovarian, uterine and systemic pathophysiological changes, although not all fully elucidated. These alterations contribute to reduced oocyte and embryo quality, reduced uterine receptivity and systemic inflammatory responses. Various guidelines recommend lifestyle interventions based on dietary and/or physical activity targeting at a 5 to 10% reduction in body weight as an initial step prior to fertility treatment for women with infertility and overweight or obesity. However, evidence from well powered randomised controlled trials (RCTs) assessing the effectiveness of lifestyle interventions aiming at weight loss prior to fertility treatments is scarce and not unequivocally positive with respect to reproductive outcomes. First, this presentation will focus on the effectiveness of pre-conception lifestyle intervention targeting weight loss, on reproductive outcomes documented in the latest systematic review (SR) and meta-analysis and preliminary results of an individual participant data meta-analysis (IPDMA). The latest SR in 2021 (Obesity reviews DOI: 10.1111/obr.13325) including 15 RCTs until March 2020 (N = 1852 women) suggests more weight loss in the intervention group. An increase in live birth rates (LBR) in nine RCTs (N = 1203 women) and a higher natural conception rate following lifestyle intervention compared to no intervention were reported. However, no effect of lifestyle intervention preceding ART in six RCTs (N = 1040 women). With respect to potential harm of lifestyle intervention there is no significant increased risk of early pregnancy loss. Complications during pregnancy, such as early pregnancy loss and maternal, fetal and neonatal outcomes are underreported in most included studies. The VENUS IPDMA (BMJ Open 2022;12:e065206) analyzed individual patient data of 11 RCTs of 14 eligible RCTs (N = 1903 participants; 1010 in the intervention group and 893 in the control group). Preliminary data (abstract ESHRE 2023) showed that physical activity and/or dietary interventions prior to fertility treatment resulted in more weight reduction compared to those in the control group in 11 RCTs. The intervention group, however, did not have a significantly higher rate of LBR in nine RCTs (N = 1702 participants). Compared to the control group, the intervention group had smaller waist and hip circumference, lower systolic and diastolic blood pressure, and lower triglycerides, total cholesterol, glucose, and insulin levels at the time of study follow up. Do we have a definitive answer to the question: “weight loss interventions prior to fertility treatment; does it make sense” using data of IPDMA? Shortcomings of the available evidence regarding the effectiveness and safety of dietary and/or physical activity interventions in women with overweight or obesity prior to fertility treatments will be presented. Limitations of the studies and future perspectives and challenges in this field of research will be highlighted. Finally, the question “does it make sense” is broader than the effectivity of the intervention. Do we as clinicians adopt our role as health advocates to advice and guide future parents to adopt a healthy lifestyle, with weight reduction as a result? Could this lead to a healthier lifestyle for the future of parents and children? To conclude: “does it make sense” is not an easy question to answer.

Anti-diabetic Activity of Spirulina and Chlorella in In vivo Experimental Rats

The effects of supplying experimental rats with unicellular green algae Chlorella and tiny filamentous cyanobacteria Spirulina, on type 2 diabetes (T2DM) were examined in the present study. Eight sets of male Sprague-Dawley albino rats, each with six individuals, were used in the investigation. Throughout the trial, Group 1 was the negative control group and was given saline regularly. Group 2 was given alloxan to induce diabetes. Spirulina was given to groups 3, 4, and 5 at dosages of 100, 200, and 300 mg/kg body weight, respectively, after diabetes induction. Similarly, groups 6, 7, and 8 received dosages of 100, 200, and 300 mg/kg body weight of Chlorella, respectively. The findings indicated that the control group had significantly higher levels of triglycerides, low-density lipoprotein (LDL), blood sugar, and very low-density lipoprotein (VLDL) and considerably lower levels of insulin, high-density lipoprotein (HDL), and phospholipids. However, rats given Spirulina (groups 3, 4, and 5) showed notably higher insulin, HDL, and phospholipids levels and significantly lower blood glucose, cholesterol, VLDL, LDL, and triglycerides levels. Rats fed with Chlorella (groups 6, 7, and 8) also showed increased effectiveness of feed ratios, greater final weights, and body weight growth percentages compared to the control group. The present study shows that supplementing with Spirulina and Chlorella improves insulin lipid patterns, blood sugar, and type 2 diabetes in vivo laboratory rats. According to the research, Spirulina and Chlorella may be used as functional meals to help control and cure diabetes.