Reduced Body Weight Research Articles

Female rats require greater energy deficit for body weight reduction than males

Female rats require greater energy deficit for body weight reduction than males

Effects of rapid or slow body weight reduction on glucose tolerance during equivalent weight loss in rats fed high-fat diet

Effects of rapid or slow body weight reduction on glucose tolerance during equivalent weight loss in rats fed high-fat diet

Preoperative weight loss interventions before total hip and knee arthroplasty: a systematic review of randomized controlled trials.

The high co-prevalence of obesity and end-stage osteoarthritis requiring arthroplasty, with the former being a risk factor for complications during arthroplasty, has led to increasing interest in employing preoperative weight loss interventions such as bariatric surgery and diet modification. However, the current evidence is conflicting, and this study aimed to investigate the effect of weight loss intervention before arthroplasty in prospective randomized controlled trials. Four electronic databases (MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials) were searched for prospective randomized controlled trials that compared weight loss interventions with usual care from inception to October 2023 by following the PRISMA guidelines. The Cochrane risk of bias tool and GRADE framework were used to assess the quality of the studies. Meta-analyses were performed when sufficient data were available from 2 or more studies. Three randomized controlled trials involving 198 patients were identified. Two studies employed diet modification, and one study utilized bariatric surgery. All three studies reported significant reductions in body weight and body mass index (BMI), and intervention groups had fewer postoperative complications. There was no difference in the length of stay between the intervention group and the control group. Variable patient-reported outcome measures were used by different research groups. Weight loss intervention can achieve significant reductions in body weight and body mass index before arthroplasty, with fewer postoperative complications reported. Further studies with different populations could confirm the effect of these interventions among populations with different obesity characteristics.

Mitochondria targeted esculetin administration improves insulin resistance and hyperglycemia-induced atherosclerosis in db/db mice.

The development and progression of hyperglycemia (HG) and HG-associated atherosclerosis are exacerbated by mitochondrial dysfunction due to dysregulated mitochondria-derived ROS generation. We recently synthesized a novel mitochondria-targeted esculetin (Mito-Esc) and tested its dose-response therapeutic efficacy in mitigating HG-induced atherosclerosis in db/db mice. In comparison to simvastatin and pioglitazone, Mito-Esc administration resulted in a considerable reduction in body weights and improved glucose homeostasis, possibly by reducing hepatic gluconeogenesis, as indicated by a reduction in glycogen content, non-esterified free fatty acids (NEFA) levels, and fructose 1,6-bisphosphatase (FBPase) activity. Interestingly, Mito-Esc treatment, by regulating phospho-IRS and phospho-AKT levels, greatly improved palmitate-induced insulin resistance, resulting in enhanced glucose uptake in adipocytes and HepG2 cells. Also, and importantly, Mito-Esc administration prevented HG-induced atheromatous plaque formation and lipid accumulation in the descending aorta. In addition, Mito-Esc administration inhibited the HG-mediated increase in VACM, ICAM, and MAC3 levels in the aortic tissue, as well as reduced the serum pro-inflammatory cytokines and markers of senescence. In line with this, Mito-Esc significantly inhibited monocyte adherence to human aortic endothelial cells (HAECs) treated with high glucose and reduced high glucose-induced premature senescence in HAECs by activating the AMPK-SIRT1 pathway. In contrast, Mito-Esc failed to regulate high glucose-induced endothelial cell senescence under AMPK/SIRT1-depleted conditions. Together, the therapeutic efficacy of Mito-Esc in the mitigation of hyperglycemia-induced insulin resistance and the associated atherosclerosis is in part mediated by potentiating the AMPK-SIRT1 axis. KEY MESSAGES: Mito-Esc administration significantly mitigates diabetes-induced atherosclerosis. Mito-Esc improves hyperglycemia (HG)-associated insulin resistance. Mito-Esc inhibits HG-induced vascular senescence and inflammation in the aorta. Mito-Esc-mediated activation of the AMPK-SIRT1 axis regulates HG-induced endothelial cell senescence.

Once-daily oral small-molecule glucagon-like peptide-1 receptor agonist lotiglipron (PF-07081532) for type 2 diabetes and obesity: Two randomized, placebo-controlled, multiple-ascending-dose Phase 1 studies.

To investigate the effects of lotiglipron (PF-07081532), a once-daily, oral small-molecule glucagon-like peptide-1 receptor agonist, in participants with type 2 diabetes (T2D) and/or obesity. Two Phase 1 randomized, double-blind, placebo-controlled, multiple-ascending-dose studies were conducted to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of lotiglipron. Across the studies, 74 participants with T2D were treated for 28 or 42 days, and 26 participants with obesity without diabetes were treated for 42 days, following randomization to placebo or lotiglipron (target doses 10-180 mg/day, with dose titration to higher target doses). Most adverse events were mild (89.6%), with nausea the most frequently reported in both studies. There were no clinically meaningful adverse trends noted in safety laboratory tests, vital signs, or electrocardiogram parameters. In participants with T2D, lotiglipron resulted in dose-dependent reductions in mean daily glucose. The 180-mg dose was associated with least squares mean decreases from baseline in glycated haemoglobin (-1.61% [90% confidence interval {CI} -2.08, -1.14] vs. -0.61% [-1.56, 0.34] for placebo) and body weight (-5.10 kg [90% CI -6.62, -3.58] vs. -2.06 kg [90% CI -4.47, 0.36] for placebo) after 42 days; a similar magnitude of weight loss was seen in participants with obesity. The observed pharmacokinetic profile supported once-daily dosing. The profile of once-daily lotiglipron with doses up to 180 mg, as observed in these two Phase 1 studies, indicated a safety and tolerability profile consistent with the mechanism of action, with dose-dependent reductions in glycaemic indices (T2D) and body weight (both populations) after multiple doses. gov identifier: NCT04305587, NCT05158244.

Treatment of mice with maternal intermittent fasting to improve the fertilization rate and reproduction.

Maternal intermittent fasting (MIF) can have significant effects on several tissue and organ systems of the body, but there is a lack of research on the effects on the reproductive system. So, the aim of our study was to analyze the effects of MIF on fertility. B6C3F1Crl (C57BL/6N × C3H/HeN) male and female mice were selected for the first part of the experiments and were analyzed for body weight and fat weight after administration of the MIF intervention, followed by analysis of sperm counts and activation and embryo numbers. Subsequently, two strains of mice, C57BL/6NCrl and BALB/cJRj, were selected and administered MIF to observe the presence or absence of vaginal plugs for the purposes of mating success, sperm and oocyte quality, pregnancy outcome, fertility status and in vitro fertilization (IVF). Our results showed a significant reduction in body weight and fat content in mice receiving MIF intervention in B6C3F1Crl mice. Comparing the reproduction of the two strains of mice. However, the number of litters was increased in all MIF interventions in C57BL/6NCrl, but not statistically significant. In BALB/cJRj, there was a significant increase in the number of pregnant females as well as litter size in the MIF treatment group, as well as vaginal plugs, and IVF. There was also an increase in sperm activation and embryo number and the MIF intervention significantly increased sperm count and activation. Our results suggest that MIF interventions may be beneficial for reproduction in mice.

Effect of a family-based lifestyle intervention on weight reduction among Jordanian children with obesity aged 6–9 years

This study aimed to evaluate the effect of a family-based lifestyle intervention on reducing body weight among Jordanian children with obesity aged 6–9 years old. The pretest-posttest control group design was conducted among 162 children (75 in the intervention group and 87 in the control group) with obesity aged 6–9 years old at four primary schools in Jordan during the period from March 2021 to July 2021. The results found that, after the intervention, there was a statistically significant change in the F scores in the control group vs. in the intervention group (M = 37.07, SD = 2.77; M = 33.48, SD = 2.73; t (160) = 8.29, P < 0.001), where the mean BMI percentile was reduced by 2.05 in the intervention group. A significant difference was demonstrated in the median BMI percentile in the intervention and control groups post-intervention (P < 0.001). A significant difference was also noticed between the average weekly reported dietary habits and the physical activities of both the control group and the intervention group post-intervention. The findings support the effect of family-based lifestyle interventions. Healthcare providers should adopt such interventions for children living with obesity. Future study is required to evaluate the long-term effectiveness of this intervention on weight reduction.

Predicted impact of banning nonessential, energy-dense food and beverages in schools in Mexico: A microsimulation study.

Childhood obesity is a growing concern worldwide. School-based interventions have been proposed as effective means to improve nutritional knowledge and prevent obesity. In 2023, Mexico approved a reform to the General Education Law to strengthen the ban of sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools and surroundings. We aimed to predict the expected one-year change in total caloric intake and obesity prevalence by introducing the ban of NEDFBs sales in schools, among school-aged children and adolescents (6 to 17 years old) in Mexico. We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and then estimated total energy intake (TEI) per day. The TEI after the intervention was estimated under 4 scenarios: (1) using national data to inform the intervention effect; (2) varying law compliance; (3) using meta-analytic data to inform the intervention effect size on calories; and (4) using national data to inform the intervention effect by sex and socioeconomic status (SES). We used Hall's microsimulation model to estimate the potential impact on body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools. We found that children could reduce their daily energy intake by 33 kcal/day/person (uncertainty interval, UI, [25, 42] kcal/day/person), reducing on average 0.8 kg/person (UI [0.6, 1.0] kg/person) and 1.5 percentage points (pp) in obesity (UI [1.1, 1.9] pp) 1 year after implementing the law. We showed that compliance will be key to the success of this intervention: considering a 50% compliance the intervention effect could reduce 0.4 kg/person (UI [0.3, 0.5] kg/person). Our sensitivity analysis showed that the ban could reduce body weight by 1.3 kg/person (UI [0.8, 1.8] kg/person) and up to 5.4 kg/person (UI [3.4, 7.5] kg/person) in the best-case scenario. Study limitations include assuming that obesity and the contribution of NEDFBs consumed at school remain constant over time, assuming full compliance, and not considering the potential effect of banning NEDFBs in stores near schools. Even in the most conservative scenario, banning sales of NEDFBs in schools is expected to significantly reduce obesity, but achieving high compliance will be key to its success. - School-based interventions have been recognized as effective means to improve nutritional knowledge and prevent obesity-related diseases.- In December 2023, the Chamber of Representatives of Mexico approved an amendment that strengthens and updates the General Education Law (Article 75) and nutritional guidelines to ban the sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools. - We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and total energy intake (TEI) per day.- We used microsimulation modeling to predict body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools.- Our modeling study suggests that an important impact on obesity prevalence can be expected if the law is implemented and enforced as intended. - If successful, this law could serve as an example beyond Mexico on how to achieve changes in body weight through school food regulation.- An important limitation of our main scenario is that we assumed full compliance of schools with the law, yet lower compliance will reduce its impact. We also did not consider historical trends on obesity or NEDFBs consumed in schools during our 1 year simulation, and we considered only the ban impact inside schools, excluding effects near and outside schools.

Integrated transcriptome and metabolome study reveal the therapeutic effects of nicotinamide riboside and nicotinamide mononucleotide on nonalcoholic fatty liver disease

Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) have received considerable attention as anti-aging and anti-metabolic disease nutraceuticals. However, few studies have focused on their role in ameliorating hepatic metabolic disturbances. In the present study, the effects of NMN and NR on the liver of mice with nonalcoholic fatty liver disease (NAFLD) were investigated via transcriptome and metabolome analyses. NMN and NR reduced body weight gain, improved glucose homeostasis, regulated plasma lipid levels, and ameliorated liver injury, oxidative stress, and lipid accumulation in mice with HFD-induced NAFLD. Integrated transcriptome and metabolome analyses indicated that NMN and NR altered the biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and linoleic acid metabolism pathways, increased saturated fatty acid (palmitic acid, stearate, and arachidic acid) content, and increased polyunsaturated fatty acid (linoleic acid and eicosapentaenoic acid) content. Quantitative reverse transcription PCR (qRT-PCR) showed that NMN and NR primarily promoted arachidonic acid and linoleic acid catabolism via cytochrome P450 (CYP450) enzymes. This study established a theoretical foundation for the potential use of NMN and NR in future clinical settings.

Lycopene Promotes Osteogenesis and Reduces Adipogenesis through Regulating FoxO1/PPARγ Signaling in Ovariectomized Rats and Bone Marrow Mesenchymal Stem Cells

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant compound, on osteoporotic bone loss remains largely unknown. Here, we show that oral administration of LYC to OVX rats for 12 weeks reduced body weight gain, improved lipid metabolism, and preserved bone quality. In addition, LYC treatment inhibited ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon H2O2 stimulation, leading to inhibiting adipogenesis and promoting osteogenesis during bone remodeling. At the molecular level, LYC improved bone quality via an increase in the expressions of FoxO1 and Runx2 and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regulation of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for osteoporosis management.

SPIRIT: Assessing Clinical Parameters Associated with Using IDegLira in Patients with Type 2 Diabetes in a Real-World Setting in Colombia.

Insulin degludec/liraglutide (IDegLira) is a fixed-ratio combination of insulin degludec (a basal insulin) and liraglutide (a glucagon-like peptide-1 receptor agonist [GLP-1RA]). This study aimed to investigate clinical outcomes in people with type 2 diabetes mellitus (T2DM) after initiating IDegLira treatment in a real-world setting in Colombia. SPIRIT is a non-interventional, single-arm, retrospective chart review study to assess clinical outcomes in people with T2DM. Participating patients were switched from a treatment regimen of basal insulin (with or without oral antidiabetics [OADs]) and started on treatment with IDegLira a minimum of 26 ± 6weeks before the data collection start date. Data were collected from the medical records of 175 patients in ten clinical centers across Colombia. Compared with baseline, there was a significant reduction in glycated hemoglobin (HbA1c) (1.3%; 95% confidence interval [CI] -1.6 to -1.0; p < 0.0001) after 26 ± 6weeks of follow-up. The mean HbA1c at baseline and at the end of the study was 9.1% and 7.8%, respectively. In addition, IDegLira significantly reduced absolute body weight by 1kg (95% CI -1.5 to -0.5; p < 0.0001), from a mean of 76.1kg at baseline to 75.1kg after follow-up. The mean IDegLira dose at the end of the study was 21.3 U, and no severe hypoglycemic events were observed during the follow-up period. In real-world practice, initiating IDegLira in patients with T2DM previously treated with basal insulin (± OAD) was associated with improved glycemic control, reduced body weight and reduced risk of hypoglycemia. ClinicalTrials.gov identifier: NCT05324462.

AGPAT3 Deficiency Impairs Adipocyte Differentiation and Leads to a Lean Phenotype in Mice.

Acylglycerophosphate acyltransferases (AGPATs) catalyze the de novo formation of phosphatidic acid to synthesize glycerophospholipids and triglycerides. AGPATs demonstrate unique physiological roles despite a similar biochemical function. AGPAT3 is highly expressed in the testis, kidney, and liver, with intermediate expression in adipose tissue. Loss of Agpat3 is associated with reproductive abnormalities and visual dysfunction. However, the role of AGPAT3 in adipose tissue and whole-body metabolism has not been investigated. We found that male Agpat3-KO mice exhibited reduced body weights with decreased white and brown adipose tissue mass. Such changes were less pronounced in the female Agpat3-KO mice. Agpat3-KO mice have reduced plasma insulin growth factor 1 (IGF1) and insulin levels and diminished circulating lipid metabolites. They manifested intact glucose homeostasis and insulin sensitivity despite a lean phenotype. Agpat3-KO mice maintained an energy balance with normal food intake, energy expenditure, and physical activity, except for increased water intake. Their adaptive thermogenesis was also normal despite reduced brown adipose mass and triglyceride content. Mechanistically, Agpat3 was elevated during mouse and human adipogenesis and enriched in adipocytes. Agpat3-knockdown 3T3-L1 cells and Agpat3-deficient mouse embryonic fibroblasts (MEFs) have impaired adipogenesis in vitro. Interestingly, pioglitazone treatment rescued the adipogenic deficiency in Agpat3 deficient cells. We conclude that AGPAT3 regulates adipogenesis and adipose development. It is possible that adipogenic impairment in Agpat3 deficient cells potentially leads to reduced adipose mass. Findings from this work support the unique role of AGPAT3 in adipose tissue.

Effects of Laghoo Shankaprakshalana (yogic colon cleansing) on anthropometric measurements in obese individuals.

Obesity is considered as one of the major public health burden and it is predictor of cardiovascular risk factor. Yoga is a mind-body medicine helps to promote health. This study was aimed to explore whether Laghoo Shankaprashalana (LS) reduce the body weight in obese individuals. This was a single group pre-post study. A total of 40 subjects (9 Male, 31 Female) aged between 18 and 40 years were recruited. This study was conducted in government yoga and naturopathy medical college, Chennai. Subjects were practiced weekly once LS for eight weeks (eight sessions). Subjects were assessed pre and post on body weight, body mass index, waist circumference, hip circumference, waist hip ratio, pulse rate and blood pressure. Variables were analyzed using Paired sample t test except waist hip ratio, which were analyzed using Wilcoxon's signed ranks test. There was significant reduction in the body weight (p<0.001, 5.81 %), Body Mass Index (p<0.001, 5.88 %), Waist Circumference (p<0.001, 7.20 %), Hip Circumference (p<0.001, 5.04 %), and Waist Hip Circumference (p<0.001, 3.19 %) after LS. However, there was no statistical significance difference in pulse rate, blood pressure. Eight sessions of Laghoo Shankaprakshalana helps to reduces body weight, body mass index, waist circumference, hip circumference and waist hip ratio. Reduction in the waist circumference might helps to reduce the cardiovascular risk. LS may be one of the cost effective intervention that can be incorporated in the weight loss regimen.

Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and on colon physiology.

Humans/mammals obtain vitamin B1 from dietary and gut microbiota sources. Considerable amount of the microbiota generated vitamin exists in the form of thiamine pyrophosphate (TPP), and colonocytes are capable of absorbing TPP via a specific carrier-mediated process that involves the colonic TPP transporter (cTPPT; encoded by SLC44A4). Little is known about the relative contribution of SLC44A4 toward total colonic carrier-mediated TPP uptake, and its role in colon physiology. To address these issues, we generated an Slc44a4 knockout (KO) mouse model (by Cre-Lox recombination) and found a near complete inhibition in colonic carrier-mediated 3H-TPP uptake in the Slc44a4 KO compared to Wild-type-littermates (WT). We also observed a significant reduction in KO mice body weight and a shortening of their colon compared to WT. Using RNAseq and Ingenuity Pathway Analysis (IPA) approaches, we found that knocking out the colonic Slc44a4 to lead to changes in level of expression of many genes, including up-regulation in those associated with intestinal inflammation/colitis. Finally, we found that the Slc44a4 KO mice to be more susceptible to the effect of the colitogenic dextran sodium sulfate (DSS) compared to WT animals, a finding that lends support to the recent prediction by multiple genome-wide association studies (GWAS) that the SLC44A4 is a possible colitis susceptibility gene. In summary, results of these investigations show that the Slc44a4 is the predominant/only transporter involved in colonic uptake of TPP, that the transporter is important for colon physiology, and that its deletion increases susceptibility to inflammation.

Launaea fragilis extract attenuated arthritis in rats through modulation of IL-1β, TNF-α, IL-6, NF-κB, COX-2, IL-4, and IL-10.

Launaea fragilis (Asso) Pau is a Cholistan desert medicinal plant. Launaea species are used as traditional remedies against various inflammatory conditions. The current research was designed to evaluate the anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of L. fragilis (Et-LF). The plant extract was prepared by triple maceration. GC-MS screening explored the presence of various bioactive phytoconstituents including n-tetracosanol-1, 1-heptacosanol, and n-hexadecanoic acid. DPPH assay demonstrated the antioxidant potential of Et-LF. Safety profile data indicated that Et-LF was safe up to the oral dose of 5000mg/kg in female rats. Anti-nociceptive activity of Et-LF was assessed in hot plate method and acetic acid-induced writhing model and the results suggested that Et-LF had significant analgesic effects in both animal models. Carrageenan, histamine, and serotonin-induced edema models were used to estimate the anti-inflammatory effects of Et-LF and were found to prevent paw edema development dose dependently. The anti-arthritic effect of Et-LF was estimated in CFA-induced arthritic rat model. Treatment with Et-LF 125, 250, 500 and flurbiprofen (FP) 10mg/kg/day significantly attenuated the paw edema, reversed the reduced body weight, and restored the altered hematological parameters in arthritic rats. Gene expression studies revealed the significant downregulation of IL-1β, TNF-α, IL-6, NF‑κB, and COX-2, and upregulation of IL-4 and IL-10 in arthritic rats treated with various doses of plant extract. Histological evaluation of ankle joints showed that Et-LF mitigated pannus formation, infiltration of inflammatory cells, and fibrous connective tissue formation in the diseased rats. Thereof, it may be concluded that the recent study demonstrated the anti-nociceptive, anti-inflammatory, and anti-arthritic effects ascribed to the signifying presence of phytoconstituents in L. fragilis.

Strength Training Protects High-Fat-Fed Ovariectomized Mice against Insulin Resistance and Hepatic Steatosis

Menopause is characterized by a reduction in sex hormones in women and is associated with metabolic changes, including fatty liver and insulin resistance. Lifestyle changes, including a balanced diet and physical exercise, are necessary to prevent these undesirable changes. Strength training (ST) has been widely used because of the muscle and metabolic benefits it provides. Our study aims to evaluate the effects of ST on hepatic steatosis and insulin resistance in ovariectomized mice fed a high-fat diet (HFD) divided into four groups as follows: simulated sedentary surgery (SHAM-SED), trained simulated surgery (SHAM-EXE), sedentary ovariectomy (OVX-SED), and trained ovariectomy (OVX-EXE). They were fed an HFD for 9 weeks. ST was performed thrice a week. ST efficiently reduced body weight and fat percentage and increased lean mass in OVX mice. Furthermore, ST reduced the accumulation of ectopic hepatic lipids, increased AMPK phosphorylation, and inhibited the de novo lipogenesis pathway. OVX-EXE mice also showed a better glycemic profile, associated with greater insulin sensitivity identified by the euglycemic–hyperinsulinemic clamp, and reduced markers of hepatic oxidative stress compared with sedentary animals. Our data support the idea that ST can be indicated as a non-pharmacological treatment approach to mitigate metabolic changes resulting from menopause.

PCB169 exposure aggravated the development of non-alcoholic fatty liver in high-fat diet-induced male C57BL/6 mice

Polychlorinated biphenyls (PCBs) are lipophilic environmental toxicants. Epidemiological studies have established a link between PCBs and both metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Multiple studies have reported that exposure to both PCB156 and PCB126 among the 12 dioxin-like PCBs leads to the development of NAFLD. However, studies to elucidate whether PCB169 induces the development of NAFLD by constructing in vivo models have not been reported. Therefore, we evaluated the effects of exposure to PCB169 (5 mg/kg-bw) on hepatic lipid metabolism in C57BL/6 mice from control diet and high-fat diet cohorts. The results showed that PCB169 exposure reduced body weight and intraperitoneal fat mass in mice on the control diet, but the liver lipid levels were significantly increased, exacerbating NAFLD in mice on a high-fat diet. Through transcriptomics studies, it was found that PCB169 exposure induced significant up-regulation of Pparγ, Fasn, and Aacs genes involved in hepatic lipogenesis, as well as remarkable up-regulation of Hmgcr, Lss, and Sqle genes involved in cholesterol synthesis. Additionally, there was notable down-regulation of Pparα and Cpt1 genes involved in lipid β-oxidation, leading to abnormal lipid accumulation in the liver. In addition, we found that PCB169 exposure significantly activated the Arachidonic acid metabolism, PPAR signaling pathway, Metabolism of xenobiotics by cytochrome P450, and Retinol metabolism pathways, and so on. Our study suggests that PCB169 can modify gene expression related to lipid metabolism, augument lipid accumulation in the liver, and further contribute to the development of NAFLD, thereby revealing the detrimental effects associated with PCB exposure on animal growth and metabolism.

Mice with NOP2/sun RNA methyltransferase 5 deficiency die before reaching puberty due to fatal kidney damage

Background NOP2/Sun RNA methyltransferase 5 (NSUN5) is an RNA methyltransferase that has a broad distribution and plays critical roles in various biological processes. However, our knowledge of the biological functions of NSUN5 in mammals is very limited. Therefore, in this study, we investigate the role of NSUN5 in mice. Methods In the present research, we built a mouse model (Nsun5-/- ) using the CRISPR/Cas9 system to investigated the specific role of NSUN5. Results We observed that Nsun5-/- mice had a reduced body weight compared to wild-type mice. Additionally, their survival rate gradually decreased to 20% after postnatal day (PD) 21. Further examination revealed the Nsun5-/- mice had multiple organ damage, with the most severe damage occurring in the kidneys. Moreover, we observed glycogen deposition and fibrosis, along with a notable shorting of the primary foot processes of glomeruli in Nsun5-/- kidneys. Furthermore, we found that the kidneys of Nsun5-/- mice showed increased expression of the apoptotic signal Caspase-3 and accumulated stronger DNA damage at PD 21. Conclusions In our study, we found that mice lacking NSUN5 died before puberty due to kidney fatal damage caused by DNA damage and cell apoptosis. These results suggest that NSUN5 plays a vital role in preventing the accumulation of DNA damage and cell apoptosis in the kidney.

Berberine attenuates obesity-induced insulin resistance by inhibiting miR-27a secretion.

Berberine (BBR) is an alkaloid found in plants. It has neuroprotective, anti-inflammatory and lipid-lowering activity. However, the efficacy of treatment with BBR and the mechanisms through which it acts need further study. This study investigated the therapeutic effects and the mechanism of action of BBR on obesity-induced insulin resistance in peripheral tissues. High-fat-fed C57BL/6J mice and low-fat-fed C57BL/6J mice with miR-27a overexpression were given BBR intervention (100 mg/kg, po), and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed. Palmitic acid-stimulated hypertrophic adipocyte models were treated with BBR (10 μM). Related indicators and protein expression levels were examined. The AUCs of the OGTT and the ITT in the BBR intervention group were reduced significantly (p < 0.01) (p < 0.05), and the serum biochemical parameters, including FBG, TC, TG and LDL-C were significantly reduced after BBR intervention. In the invitro experiments, the triglyceride level and volume of lipid droplets decreased significantly after BBR intervention (p < 0.01) (p < 0.05). Likewise, BBR ameliorates skeletal muscle and pancreas insulin signalling pathways invivo and invitro. The results showed that BBR significantly ameliorated insulin resistance, reduced body weight and percent body fat and improved serum biochemical parameters in mice. Likewise, BBR reduced triglyceride level and lipid droplet volume in hypertrophic adipocytes, BBR improved obesity effectively. Meanwhile, BBR ameliorated the histomorphology of the pancreas, and skeletal muscle and pancreas insulin related signalling pathways of islets in invitro and invivo experiments. The results further demonstrated that BBR inhibited miR-27a levels in serum from obese mice and supernatant of hypertrophic adipocytes. miR-27a overexpression in low-fat fed mice indicated that miR-27a caused insulin resistance, and BBR intervention significantly improved the miR-27a induced insulin resistance status. This study demonstrates the important role of BBR in obesity-induced peripheral insulin resistance and suggest that the mechanism of its effect may be inhibition of miR-27a secretion.

246 The effect of trypsin inhibitor unit concentrations from raw soybeans in grower pig performance and protein digestibility

Abstract Soybeans contain two major protease inhibitors, Kunitz trypsin and Bowman-Birk protease inhibitors, both of which are anti-nutritional components that can be directly linked to a reduction in amino acid bioavailability and growth performance in swine. Therefore, the objective of this study was to determine the level at which trypsin inhibitor units (TIU, expressed as TIU/mg of complete feed), coming from raw soybeans, in pig diets result in reduction in growth performance and digestibility. This study used 45 grower gilts initial body weight (BW) = 39.7 ± 2.1 kg] that were individually penned and fed one of five dietary TIU treatments (n = 9 pigs/trt) in a complete randomized design. Diets were representative of a commercial corn-soybean meal diet and formulated to have ranging TIU/mg of complete feed of 0.89, 1.77, 3.55, 6.99, and 11.54 TIU/mg utilizing raw ground soybeans and soybean meal at incremental levels. Analyzed diets contained 0.99, 2.23, 3.07, 6.49, and 9.38 active TIU/mg. Diets were balanced to the same grams of SID Lys:ME of 2.85 and NDF concentration of 7.4% utilizing soybean oil and soybean hulls, respectively. Individual feed intake was recorded throughout, and pig BW were collected on d 0, 21, and 27 to calculate average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency gain to feed ratio (G:F). All pigs were placed into metabolism crates on d 21 for 6 d to determine apparent total tract digestibility (ATTD) of nitrogen (N), N excretion and N balance. Growth performance and ATTD data were analyzed with pig as the experimental unit and diet TIU level as a fixed effect using ANOVA, linear, and quadratic contrast models. Overall, ADG decreased as diet TIU increased (1.07, 1.03, 1.02, 0.91, and 0.83 kg/d, respectively, linear P &amp;lt; 0.001). However, no differences in ADFI (P &amp;gt; 0.10) were reported and this resulted in a decrease in G:F (0.48, 0.45, 0.43, 0.41, 0.36, respectively, linear P &amp;lt; 0.001) as dietary TIU concentrations increased from 0.99 to 9.38 TIU/mg. Compared with 0.99 TIU/mg, pigs fed 9.38 TIU/mg had a 9.32% reduction in final BW (68.7 vs. 62.3 kg, linear P &amp;lt; 0.001). Apparent total tract digestibility of N decreased when pigs were fed 9.38 TIU/mg compared with 0.99 and 2.23 TIU/mg (83.26% vs. 90.29% and 89.57%, respectively, P &amp;lt; 0.001). In conclusion, as total trypsin inhibitor units increase in complete feed of grower pigs, digestibility of protein, growth rates and feed efficiency are reduced in a linear manner.