Leptin

Treatments for type 2 diabetes mellitus (DM2) are not universally effective, underscoring the need for new therapeutic alternatives. Extracts of Echeveria subrigida have demonstrated potent in vitro activities, such as antioxidant and α-glucosidase inhibitory effects, as well as in vivo activities, including hypoglycemic, antihyperglycemic, immunomodulatory, and adaptogenic effects.

The present study aimed to investigate the antidiabetic mechanisms of ethanolic (EEEs) and methanolic (MEEs) extracts of E. subrigida , standardized for isorhamnetin-3-O-glucoside (I3G), in streptozotocin (STZ)-induced diabetic rats.

The E. subrigida extracts, EEEs and MEEs, were obtained by maceration and standardized for the content of I3G. The antidiabetic effect was evaluated using STZ-induced diabetic rats, which were randomly allocated to experimental groups (n = 6). Isorhamnetin (ISO) and metformin (MET) treatments served as positive controls. Parameters were measured at least in triplicate, and means were compared using the Fisher test (P < 0.05). The following evaluations were conducted: Levels of monocyte chemoattractant protein-1 (MCP-1), leptin, and inflammatory-related cytokines in serum; expression of proteins in the phosphatidylinositol 3-kinase (PI3K) and adenosine monophosphate-activated protein kinase (AMPK) pathways; transcriptional expression of peroxisome proliferator-activated receptor alpha (PPARα) and sterol regulatory element-binding protein 1c (SREBP-1c) in liver tissue; and histology of the liver and pancreas.

All treatments, except ISO, demonstrated antidiabetic effects, with glucose levels in MET (183.75 ± 61.89 mg/dL) and MEEs (168.00 ± 48.10 mg/dL) rats comparable to healthy control (HC) rats (109.25 ± 6.11 mg/dL). Leptin levels decreased in diabetic control (DC) rats (0.17 ± 0.07 ng/mL), while levels in the EEEs (0.65 ± 0.06 ng/mL) and MEEs (0.77 ± 0.09 ng/mL) groups were similar to those of the HC group (0.71 ± 0.19 ng/mL). The levels (pg/mL) of cytokines (IL-10, IL-6, IFN-γ, and IL-4) were elevated in DC rats (72.26 ± 12.91, 36.72 ± 2.91, 4.56 ± 0.63, and 16.34 ± 2.06, respectively), but were effectively reduced in rats treated with EEEs (29.64 ± 2.86, 9.85 ± 2.92, 1.11 ± 0.24, and 6.71 ± 1.15, respectively) and MEEs (26.65 ± 5.31, 7.30 ± 1.89, 1.25 ± 0.28, and 5.55 ± 0.43, respectively). Liver histology showed nearly normal structures, although pancreatic histology revealed hypertrophied Langerhans islets across all DM2 groups. The Akt activation and inactivation of AS160 by phosphorylation were detected in the livers of EEEs and MEEs rats without AMPK activation. Additionally, these groups expressed the SREBP-1c mRNA.

The EEEs and MEEs exhibited antidiabetic activity via the PI3K/Akt pathway, suggesting E. subrigida as a potential preventive or therapeutic agent for type 2 diabetes.

This study aimed to evaluate the effects of pre-conditioning exercise on body lipid metabolism, leptin secretion, and the downstream pathways at the early stage of type 2 diabetes mellitus (T2DM).

The T2DM model was established using an 8-week high-sugar, high-fat diet combined. The T2DM model was established using an 8-week high-sugar, high-fat diet combined with streptozocin (STZ) injection. Two exercise interventions, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) were performed during the model-building process. One week following the STZ injection, rats were euthanized. Blood, gastrocnemius muscle, and epididymal fat pad were collected. Plasma leptin content was measured by ELISA. The expression of leptin-mRNA in epididymal adipose tissue was measured using RT-qPCR, and its protein expression was detected by a western blot. Leptin, leptin-R, and AMPK (AMP-activated protein kinase) - ACC (Acetyl-CoA carboxylase) expression in gastrocnemius muscle was also detected by western blot. Free fatty acids (FFA) and triglycerides (TG) contents in gastrocnemius muscle were measured using a biochemical assay.

In the HIIT group, glucose tolerance and leptin receptor expression increased, as did the expression and phosphorylation of AMPK protein. At the early stage of T2DM, it increased significantly in the gastrocnemius muscle in the MICT group.

At the early stage of T2DM, pre-conditioning exercise in the form of HIIT was found to inhibit the leptin-mRNA expression in adipose tissue, suppress leptin synthesis, up-regulate AMPK-ACC signaling pathway, and promote lipid decomposition in skeletal muscle tissue. Pre-conditioning of MICT led to the accumulation of FFA and TG in skeletal muscle, likely due to exercise adaptation rather than ectopic deposition of lipids.

Many studies have shown that asthma is characterized by inflammation of the airway and infiltration of eosinophil cells (EOSCs). It has also shown that during pregnancy, the level of leptin, as a regulator of immune responses, increases with the progression of the pregnancy process. In this study, the effect of asthma on inflammatory factors was evaluated in the lung and uterine tissues of asthmatic pregnant or non-pregnant mice.

In this experimental study, 40 female Balb/c mice (8 weeks old) were classified into 4 groups, and asthma by ovalbumin (OVA) at a concentration of 20 μg/100μl was induced. Lung and uterus tissues were histopathologically evaluated for the presence of inflammation. The level of leptin hormone in blood serum was investigated using an indirect enzyme-linked immunosorbent assay (ELISA). Also, Interleukin-8 (IL-8), forkhead box protein 3 (Foxp3), eosinophil chemotactic protein (eotaxin), and mucin 5AC (Muc5ac) gene expression were measured in respiratory and uterine cells by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) assay (P<0.05, P<0.01 and P<0.001). 

Morphological assessment of inflammation in lung tissue showed a significant increase in asthmatic groups compared to healthy groups. Hormone measurement revealed a significant rise in leptin levels in pregnant groups compared to non-pregnant groups. Also, the expression level of IL-8, Foxp3, eotaxin, and Muc5ac genes increased in pregnancy compared to negative control.

In asthma, inflammation rate increases at the cellular and molecular levels, and the leptin increment might have an influence on the inflammation.

The objective of the study was to find out the influence of Thioflavin-T (ThT) on obesity and fatty liver by investigating the adipokine hormones, and insulin serum level of male NMRI mice which were exposed to a high-fat diet (HFD).

50 adult male NMRI mice were separated into five groups: n=10. The control group was given a standard diet at twelve-week intervals. The sham group was nourished with HFD that lasted for 8 weeks, afterwards, the group received a standard diet and solvent water (0.5ml) by gavage (4 weeks). The experimental groups 1-3 were nourished with HFD (4% cholesterol, 60% fat) eight-week period. Then, the treatment period started in experimental groups by receiving a normal diet in addition to ThT with three doses (5,10 and 15 mg/kg, 0.5ml), via gavage (4 weeks). 

HFD contributed to a substantial reduction in serum adiponectin levels and increased leptin serum in the sham group opposite to the control group (P< 0.001). However, the concentration of both adipokine hormones was significantly modified under the treatment of ThT in a dose-dependent manner. Insulin serum increased in the sham group significantly (P< 0.001), meanwhile, a significant decrease was shown in experimental groups 2, and 3 than in the sham group (P<0.01). ThT also reduced HOMA-IR in experimental groups. The introduction of ThT in varying doses led to the induction of polymorphonuclear cells in the liver tissue.

Our findings propose that ThT can affect liver function and body weight by modulating the serum levels of adipokine hormones besides decreasing the level of insulin and HOMA-IR in mice fed with HFD.

Infertility affects about 15% of couples during reproductive age and male factor infertility accounts for half of these cases. This study aimed to evaluate the expression of leptin, KISS1, leptin receptor, and HOTAIR genes in blood and semen samples of individuals diagnosed with oligospermia in comparison to healthy controls.

In the current investigation, we studied 36 semen and 30 blood samples from fertile oligospermic men as well as the same number of healthy controls. RNA was extracted and cDNA was synthesized. Real-time polymerase chain reaction (PCR) was conducted to assess the gene expression levels. Statistical analysis was performed using Graph Pad Prism software. The results were reported as mean±SEM and any P< 0.05 were considered statistically significant.

A significant increase in the expression of the leptin gene in infertile males, particularly in semen samples (P< 0.001) was found when compared to the healthy controls. On the other hand, significant decrease in the expression of the KISS1 (P< 0.0001) and HOTAIR (P< 0.001) genes, particularly in semen samples were found when compared to the controls. As it was shown, the expression of leptin receptor had no significant effects on male infertility. Additionally, there may be a potential correlation between the expression of HOTAIR and the leptin and KISS1 genes, with a negative correlation observed between HOTAIR and leptin, and a positive correlation between HOTAIR and KISS1 in both blood and semen samples. However, further investigations are necessary to establish the statistical significance of these correlations.

According to the results, leptin, KISS1, and HOTAIR genes seem to be affected in oligospermia, however, further studies with higher sample sizes are necessary.

Primary infertility affects a significant proportion of couples and is often attributed to female factors. Obesity, which is associated with increased levels of the hormone leptin, is a known risk factor for female infertility. The present study was conducted with aim to investigate the association between BMI and leptin levels in females with primary infertility.

This cross-sectional study was performed on 100 women with primary infertility at Al-Nuaman Hospital and Al-Salama private hospital from September 2022 to March 2023. The participants were divided into four groups: Group 1 (normal weight, fertile), Group 2 (overweight infertile), Group 3 (obese infertile), and Group 4 (severely obese infertile) women, each consisting of 25 participants, categorized based on their BMI: normal BMI (18.5–24.9 kg/m²), overweight BMI (25–29.9 kg/m²), obesity BMI (≥30 kg/m²), and severely obese BMI (35-40 kg/m²). The mean leptin levels were compared between the four groups using ANOVA, and the association between BMI and leptin levels was assessed using Pearson''s correlation coefficient.

There was a highly significant correlation between primary infertility and the parameters (BMI and leptin) (P

Osteoporosis, characterized by diminished bone mass and increased fracture susceptibility, prompts the investigation into the impact of a four-month TRX training regimen on femur neck bone mineral density (BMD) and its correlation with serum leptin levels in women with osteopenia.

In this quasi-experimental study, 30 women with osteopenia were purposefully selected and randomly assigned to TRX training (n = 15) or control (n = 15) groups. The intervention group underwent TRX exercises thrice weekly for 45-60 minutes per session for four months. Blood samples collected at baseline and post-intervention measured serum leptin levels via ELISA kit (Bio vendor, Czech Republic), while Dexa Lexxos Digital (2D model, USA) determined femur neck BMD. SPSS 20 software, dependent/independent samples t-tests, and Pearson correlation were used for data analysis.

TRX training significantly increased femur neck BMD, reducing serum adiponectin levels versus the control group (P = 0.001 and P = 0.01, respectively). Compared to baseline, TRX training raised femur neck BMD and lowered serum leptin levels (P = 0.000 and P = 0.01, respectively). A significant inverse correlation emerged between femoral neck BMD and serum leptin levels in women with osteopenia (P = 0.00).

Findings suggest that TRX resistance training holds promise for enhancing the rehabilitation of women with osteopenia

Type 2 DM is a heterogeneous group of disorders characterized by insulin resistance, impaired insulin secretion, increased glucose production, and abnormal fat metabolism. Diabetes mortality primarily results from microvascular complications such as diabetic retinopathy, nephropathy, and neuropathy, as well as macrovascular complications like coronary artery, peripheral vascular, and cerebrovascular diseases. Patients with diabetes usually have changes in adipose tissue metabolism and abnormalities in the secretion of adipokines such as leptin. The present study aims to study the relationship between serum leptin levels and lipid profile parameters among non-obese type 2 diabetes mellitus patients and non-diabetic individuals.

This hospital-based cross-sectional study was conducted among 41 type 2 diabetic patients and 41 non-diabetic individuals of both sexes between the ages of 40 and 70. Fasting blood glucose (FBS), serum leptin, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL) levels were assayed.

The mean serum leptin levels among diabetic patients were lower than those of non-diabetic individuals, and this difference in mean was statistically significant. The study showed a significant negative correlation between serum leptin, TC, TG, and low-density lipoprotein (LDL), and a positive correlation with HDL. In the final regression model, serum leptin showed a statistically significant association with FBS and HDL.

This study demonstrated that serum leptin levels can be a strong predictor of low HDL levels in diabetic patients. It can also contribute to raised levels of total cholesterol, triglyceride, and LDL, which are responsible for macrovascular complications in diabetics.

Vitamin D, crucial for bone health and calcium homeostasis, also impacts metabolic processes and endocrine functions. It may influence leptin, a key hormone regulating energy balance. This meta-analysis evaluates the effect of vitamin D supplementation on serum leptin concentrations, addressing inconsistencies and exploring its potential role in metabolic health.

This review examined supplementation with vitamin D, alone or with calcium, as an intervention for its effects on serum leptin concentrations. Following PRISMA guidelines, a comprehensive search of electronic databases up to March 2024 identified eligible trials. Eleven randomized clinical trials were included, assessing vitamin D supplementation versus placebo or control. The meta-analysis, registered in PROSPERO (www.crd.york.ac.uk/ PROSPERO/ CRD42020177472), used STATA for statistical analysis, with outcomes reported as mean differences (MD) and 95% confidence intervals (CIs).

Initially, 503 studies were identified, with 366 excluded after screening. Ultimately, 11 studies with 819 participants were included. Trials varied in vitamin D dosage, frequency, and whether calcium was included. Pooled analysis found no significant effect of vitamin D on leptin concentrations (MD: -0.13, 95% CI -1.12 to 0.87). Subgroup analyses showed no differences based on intervention duration or calcium inclusion.

Our meta-analysis demonstrated that vitamin D supplementation does not significantly affect serum leptin levels, adding to the existing evidence on vitamin D metabolic roles. Further research is crucial to unravel the interaction between vitamin D and adipokines like leptin, given widespread vitamin D deficiency and its metabolic implications.

Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on bone and bone-related diseases including osteoporosis, in this study, we aimed to conduct a systematic review of various studies on the effect of leptin on osteoporosis, which may find an answer to the existing ambiguities.

The search was performed to review studies on the effects of leptin on osteoporosis by using several databases including Scopus, PubMed, Web of Science, and Google Scholar. Electronic searches were conducted on 5 Jan 2023. There was no limit on the publication date of the articles. The risk of bias for the animal study was assessed with the CAMARADES checklist, and the study quality assessment was also assessed based on the guidelines for in vivo experiments (ARRIVE). In this study, the risk of bias (quality) of human studies was assessed using the quality assessment checklists by NHLBI.

Overall, 34 articles were included for data extraction and quality assessment. Overall, 27 human studies and seven animal studies were included in the article. The results of most of the studies conducted in this study showed that leptin has a physiological role in maintaining bone mass and better bone quality and reduces bone marrow adipogenesis and increases bone mineral density (BMD). As plasma leptin levels increased, BMD values or bone formation biomarkers increased.

Leptin has an inhibitory role against bone resorption and increasing osteoprotegerin (OPG) levels, which, as a result, maintains bone density and reduces osteoclast activity, and has a positive relationship with increasing osteocalcin.

Adipose tissue-derived adipokines affect cardiometabolic health. This study aimed to evaluate the effect of interval resistance training with different intensities on leptin, adiponectin, and acrosin levels in obese males.

Fourty-four obese males (27.70± 3.02 years) were randomly allocated into four groups: high intensity (HI), moderate intensity (MI), low intensity (LI), and control (C). Subjects of the HI, MI, and LI groups implemented the training program for 12 weeks, three sessions a week with intensities corresponding 80% 1RM, 60% 1RM, and 40% 1RM,, respectively. Body composition and plasma levels of leptin, adiponectin, and asprosin were evaluated before and after interval resistance training at different intensities.

Following exercise, serum levels of leptin and asporin were significantly reduced in all groups (P< 0.01). The greatest reduction of leptin and asporin levels was recorded in the HI group (P= 0.001, P= 0.01) for leptin and asporsin levels, respectively. The level of adiponectin significantly decreased after exercise in all groups (P< 0.001, F= 12.44). The greatest reduction was observed in the HI group compared with the MI and UI group (P= 0.001).

Interval resistance training with different intensities can cause significant changes in leptin, asprosin, and adiponectin levels in obese men, and this improvement was better at high intensities.