Decrease In Leptin Research Articles

Fustin Ameliorates Elevated Levels of Leptin, Adiponectin, Serum TNF-α, and Intracellular Oxidative Free Radicals in High-Fat Diet and Streptozotocin-Induced Diabetic Rats.

Fustin is a prominent ingredient of Rhus verniciflua Stokes (Anacardiaceae) and has a wide range of pharmacological and clinical effects. The present study attempted to evaluate the antidiabetic potential of fustin in streptozotocin- and high-fat diet-induced diabetes in rats. The efficacy of fustin 50 mg/kg and 100 mg/kg/day p.o. was studied in 60% of total calories from fat as a high-fat diet along with single-dose administration streptozotocin (50 mg/kg, i.p.) experimentally induced diabetes in rats for 42 days. The mean body weight; blood glucose; and biochemical parameters such as lipid profile, total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), insulin, leptin levels, adiponectin levels, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity in serum were measured. The rats’ weight was maintained in the fustin groups compared to the diabetic control group. Diabetes caused a significant increase in serum levels in blood glucose, lipid profile, MDA, TNF-α, ALT, and AST parameters and a decrease in serum insulin, adiponectin, leptin, GSH, SOD, and CAT compared to healthy rats. The treatment regimen with fustin (50 and 100 mg/kg) significantly restored all serum parameters in test groups. The present study found clinical evidence for the first time regarding the significant antidiabetic property of fustin, which could be a worthwhile candidate for the treatment of diabetes.

OS05.9.A Short-term fasting in glioma patients - Analysis of diet diaries and metabolic parameters of the ERGO2 trial

Abstract BACKGROUND The prospective, randomized ERGO2 trial investigated the effect of fasting / calorie restricted ketogenic diet (KD-IF) on re-irradiation for recurrent brain tumors (Clinicaltrials.gov number: NCT01754350). The study did not meet its primary endpoint of improved progression-free survival in comparison to a standard diet (SD). We here report the results of the quality of life questionnaire, neurocognition testing, detailed analysis of the diet diaries and the alterations of metabolic parameters. MATERIAL AND METHODS 50 Patients were randomized 1:1 to re-irradiation combined with either SD or KD-IF. The KD-IF schedule included 3 days of ketogenic diet (KD: 21–23 kcal/kg/d, carbohydrate intake limited to 50 g/d), followed by 3 days of fasting and again 3 days of KD. Follow-up included examination of cognition, quality of life and serum samples. RESULTS The 20 patients who completed KD-IF met the prespecified goals for calorie and carbohydrate restriction. In these, a decrease in leptin and insulin and an increase in uric acid was observed. The SD group had a lower calorie intake of 21 kcal/kg/d than the expected 30 kcal/kg/d. Neither quality of life nor cognition were affected by the diet. Low glucose emerged as a significant prognostic parameter in a best responder analysis. CONCLUSION The strict caloric goals of the ERGO2 trial could be achieved by patients with recurrent brain tumor. The unexpected lower calorie intake of the SD group might have hampered the interpretation of the trial. However, the short diet schedule already led to significant metabolic alterations, suggesting that short-term dietary interventions might be therapeutically useful, possibly combined with other modalities.

Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial

PurposeThe prospective, randomized ERGO2 trial investigated the effect of calorie-restricted ketogenic diet and intermittent fasting (KD-IF) on re-irradiation for recurrent brain tumors. The study did not meet its primary endpoint of improved progression-free survival in comparison to standard diet (SD). We here report the results of the quality of life/neurocognition and a detailed analysis of the diet diaries.Methods50 patients were randomized 1:1 to re-irradiation combined with either SD or KD-IF. The KD-IF schedule included 3 days of ketogenic diet (KD: 21–23 kcal/kg/d, carbohydrate intake limited to 50 g/d), followed by 3 days of fasting and again 3 days of KD. Follow-up included examination of cognition, quality of life and serum samples.ResultsThe 20 patients who completed KD-IF met the prespecified goals for calorie and carbohydrate restriction. Substantial decreases in leptin and insulin and an increase in uric acid were observed. The SD group, of note, had a lower calorie intake than expected (21 kcal/kg/d instead of 30 kcal/kg/d). Neither quality of life nor cognition were affected by the diet. Low glucose emerged as a significant prognostic parameter in a best responder analysis.ConclusionThe strict caloric goals of the ERGO2 trial were tolerated well by patients with recurrent brain cancer. The short diet schedule led to significant metabolic changes with low glucose emerging as a candidate marker of better prognosis. The unexpected lower calorie intake of the control group complicates the interpretation of the results.Clinicaltrials.gov number: NCT01754350; Registration: 21.12.2012.

Aerobic Versus Resistance Training: Leptin and Metabolic Parameters Improvement in Type 2 Diabetes Obese Men

ABSTRACT Purpose: The purpose of the research was to determine the changes in metabolic parameters, leptin, and irisin levels after aerobic and resistance training in type-2 diabetes obese men. Methods: Forty-five participants in the age range of 17–25 years were randomized into three groups: aerobic training (AT), resistance training (RT), and control (CO). All training sessions were fulfilled 4 days per week for two months. The aerobic training began with intensity of 65% of the maximum aerobic power and finished with 90%. The resistance program started with 50% of one-repetition maximum and reached 70% in the 8th week. Results: Factorial analysis of variance and Bonferroni post-hoc test revealed significant decreases in leptin (p = .043), fasting blood sugar (FBS) (p = .023), insulin (p = .001), homeostasis model assessment for insulin resistance (HOMA-IR) (p = .022) in AT compared with CO and insulin (p = .006) in AT compared with RT. The change of percent body fat (PBF) was positively correlated only with change of HOMA-IR in AT group (p = .032) at p < .05. Conclusion: The result suggests that, compared to resistance training, aerobic training can control metabolic situations such as insulin resistance through the leptin hormone function, and not irisin in type-2 diabetes obese men.

Continuous energy restriction (CER) plus 16/8 time-restricted feeding improve body composition and metabolic parameters in overweight and obese, but no more than CER alone

BACKGROUND: Current guidelines recommend continuous energy restriction (CER) and lifestyle change as the basis of obesity treatment. Recently, several intermittent fasting protocols have received considerable interest as an alternative weight loss strategy. OBJECTIVE: This study compared the effects of 8-week CER versus CER along with 16/8 time-restricted feeding (16/8 TRF) on body composition and metabolic markers in excess weight physically active subjects. METHODS: Twenty-four physically active obese or overweight adults, from both genders, were split into two groups: CER plus 16/8 TRF (CER + TRF) and CER. Both groups consumed a 20%energy restriction diet. CER plus 16/8 TRF were asked to consume their meals during an 8-hour open window (12 to 20 pm). We evaluated body composition and metabolic biomarkers before and after the intervention. RESULTS: We observed a reduction in body weight (BW), body mass index (BMI), waist circumference (WC), and fat mass (FM) in both groups. However, a decrease in fat-free mass (FFM) and skeletal muscle mass (SMM) was seen only in the CER. Although fasting glucose did not change, we observed a decrease in fasting insulin and HOMA-IR in both groups. Leptin decrease in both treatments. Cortisol levels increased only in the CER group. CONCLUSIONS: We can conclude that CER + TRF is as effective as CER to promote weight and fat loss, but, CER + TRF seems to be more efficient in maintaining lean body mass.

Effect of Administration of Flavonoid-Rich Extract from Hibiscus sabdariffa to Lactating Rats on Plasma Glucocorticoid, Leptin, and Postnatal Growth of Offspring

Introduction: Flavonoids are a group of natural substances with variable phenolic structures well-known for their beneficial effects on health. Flavonoids are now considered an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal, and cosmetic applications because of their anti-oxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Aim: This study was aimed at investigating the effect of administration of flavonoids from Hibiscus sabdariffa (HS) to lactating rats on plasma glucocorticoids, leptin, and postnatal weights of the offspring. Materials and Methods: Forty pregnant female Sprague − Dawley rats weighing 150 g–200 g were used for this study. Flavonoids were extracted from HS following standard procedures. On the day of delivery, the rats were divided basically into four groups of 10 dams per group. Group A received tap water; Group B received low dose of flavonoid (5 mg/kg body weight daily); Group C received medium dose of flavonoid (10 mg/kg body weight daily); and Group D received high dose of flavonoid (20 mg/kg body weight daily). Flavonoid administration commenced on day 1 of lactation and ended at weaning. Dams from each group had their blood withdrawn from the orbital sinus on days 1, 7, and 21 for assay of plasma glucocorticoids and leptin. Food intake of the dams and body weight of the offspring was measured. Results: There was a progressive dose-dependent decrease (P &lt; 0.05) in maternal plasma glucocorticoids and leptin with the most decrease seen in the high dose group and PND 21. Low dose flavonoid caused a progressive decrease in maternal food consumption when compared with the control group (P &lt; 0.05). Low dose extract caused a progressive decrease in the body weight of the offspring, whereas the high dose caused a progressive increase in the body weight of the offspring (P &lt; 0.05). Conclusion: Flavonoids from HS caused a progressive decrease in glucocorticoids and leptin with a resultant progressive increase in maternal food intake and body weights of the offspring.

EFFECT OF OBESTATIN ON PITUITARY GONADAL AXIS, LEPTIN AND MDA LEVELS IN OBESE SPRAGUE DAWLEY RATS

Objective: To determine the effect of obestatin administration on FSH, LH, testosterone, leptin and MDA levels in obese Sprague Dawley Rats.&#x0D; Study Design: Laboratory based animal study.&#x0D; Place and Duration of Study: Physiology department, Army Medical College Rawalpindi, from Mar to Jun 2015.&#x0D; Methodology: This randomized controlled trial was conducted at Physiology Department Army medical college. Male healthy Sprague Dawley rats were randomly divided into 3 groups (n–15 each) i.e. control group (group I) fed with normal pellet diet (NPD), obese group (group II) and obestatin treated obese group (group III) fed with high fat diet (HFD). After 10 weeks, group III was treated with obestatin (1nmol/100ml intraperitoneally). Blood samples were obtained by terminal intracardiac sampling for bioasssays of FSH, LH, testosterone, leptin and MDA by ELISA.&#x0D; Results: Obestatin supplementation in obese rats showed significant increase in LH levels (3.79 ± 0.05) and testosterone levels (2.07 ± 0.22) when compared to the non treated obese rats (2.19 ± 0.07) and (1.37 ± 0.15) respectively while significant decrease in leptin (3.85 ± 0.23) and MDA levels (1.62 ± 0.07) was observed when compared to the non-treated control groups (6.10 ± 1.18) and (1.95 ± 0.07) respectively. However, serum FSH levels remained unchanged among the treated and nontreated groups.&#x0D; Conclusion: Obestatin increases the testosterone levels by augmenting the pituitary gonadal axis through decrease in the oxidative stress and leptin levels in obese rats.

Circulating leptin, soluble leptin receptor and free leptin index in critically ill patients with sepsis: a prospective observational study.

Leptin, the prototype adipokine, exerts immunomodulatory actions being implicated in inflammatory responses during sepsis. Clinical evidence regarding its role in sepsis has been contradictory, while free leptin has not been studied. The aim of this study was to jointly investigate circulating total leptin, its soluble receptor (sOB-R), and free leptin, as well as their kinetics in critically ill patients with sepsis regarding their diagnostic and prognostic value. In a prospective study, serum total leptin, sOB-R and free leptin index (FLI) were determined in 102 critically ill patients with sepsis within 48 hours from sepsis onset and one week after enrollment, and in 102 age and gender-matched healthy controls. Upon enrolment, total leptin, sOB-R and FLI were significantly higher in septic patients compared to controls and they were positively correlated with sepsis severity scores, while they presented a significant decrease during the first week (P<0.001). The decrease in total leptin and sOB-R was significantly higher in patients with sepsis compared to septic shock and in survivors compared to non-survivors at 28 days (P<0.001). Higher serum total leptin was independently associated with survival at 28 days (enrollment: HR 0.86, P=0.03; one week after: HR 0.77, P<0.001). Higher kinetics of total leptin (but not FLI) was independently associated with survival after adjustment (HR: 0.48, P=0.001). Higher circulating total leptin and its higher kinetics during the first week from sepsis onset independently predict 28-day survival in critically ill patients. Free leptin did not present any additional diagnostic and prognostic value in sepsis.

Effect of Reduction Mammoplasty on Insulin and Lipid Metabolism in the Postoperative Third month: Compensatory Hip Enlargement.

BackgroundsThe positive effects of reduction mammoplasty on metabolic profile have been shown in a limited number of studies. This study objective to reveal the effects of reduction mammoplasty on metabolic profile and anthropometric measurements.Subjects and MethodThe study was prospectively conducted on 42 patients who were operated between April 2019 and March 2020. Fasting plasma glucose, fasting plasma insulin, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein cholesterol, HgA1c, homeostasis model assessment scores, adiponectin, leptin, and resistin levels were evaluated. In addition, age, height, weight, body mass index; breast, chest, waist, hip circumference; waist-hip ratio, and bilateral breast resection tissue weights were recorded. Data and blood samples were collected one hour before the operation, 6 and 12 weeks after the operation.ResultThe patients' mean age was 43.14±10.24, and their average height was 159.42±4.96 cm. The excised bilateral dermo fatty tissue weight was 1435.85±721.16 g. At the postoperative 40th day a decrease in leptin (p = 0.001), resistin (p =0.008), glucose (p = 0.021) and insulin resistance values (p=0.013) stated. There was an increase in adiponectin (p < 0.001) and HDL (p = 0.013) levels at the postoperative 40th day. In the postoperative third month, these data returned to the previous levels that were measured before operations. However, an increase in hip circumference (p = 0.034) and a decrease in waist-hip ratio (p < 0.001) was detected in third month. Also, there was no difference in body mass index and weight compared to pre-operation.ConclusionAfter reduction mammoplasty, compensatory fat growth in the hip area, an increase in the hip circumference, and a decrease in the waist-hip ratio were observed in the postoperative third month.Level of EvidenceThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Beneficial effects of Se/Zn co-supplementation on body weight and adipose tissue inflammation in high-fat diet-induced obese rats.

This research investigated the effect of co‐supplementation of selenium with zinc on weight control and the inflammatory and oxidative status in relation to obesity. Male Wistar rats (N = 32) were randomly divided into four groups after induction of obesity model: 1) “Zn” was supplemented with zinc sulfate (15 mg/kg BW), 2) “Se” supplemented with selenium as sodium selenate (0.5 mg/kg BW), 3) “Zn + Se” which received Zn (15 mg/kg BW) + Se (0.5 mg/kg BW), and 4) “HFD” as the control group. The intervention was done for eight weeks. At the end of treatment, serum and tissue level of Zn, Se, SOD, GSH‐Px, MDA, leptin, TNF‐α, and IL‐6 was evaluated. Weight and food intake were significantly reduced in the Se group(p < .001), while in the Zn group, weight gain due to obesity was prevented compared to the control group (p = .48). There was a significant and stronger increase in SOD, GSH‐Px levels and a remarkable decrease in MDA, leptin, TNF‐α, and IL‐6 in the group receiving the combination of two supplements than either alone(p < .001). Leptin had a positive correlation with inflammatory factors and lipid peroxidation marker and showed an inverse relationship with Zn and Se levels and anti‐oxidative enzymes(p < .05). The analysis showed the mediating role of leptin in the effects of zinc. Co‐supplementation of selenium and zinc may have a synergistic effect in reduction of oxidative and inflammatory markers. Regarding the effect of zinc on inflammatory factors and lipid peroxidation, leptin can play a mediating role.

Effect of Weight Loss by Low-Calorie Diet on Cardiovascular Health in Type 2 Diabetes: An Interventional Cohort Study.

Cardiovascular disease (CVD) remains a major problem for people with type 2 diabetes (T2DM), and the leading cause of death worldwide. We aimed to determine cardiovascular benefits of weight loss with or without remission of diabetes, and to assess utility of plasma biomarkers. 29 people with T2DM were studied at baseline and after dietary weight loss. Change in plasma adipokines and lipid related markers was examined in relation to weight loss, diabetes remission, 10-year cardiovascular risk (QRISK), and duration of diabetes. QRISK decreased markedly after weight loss (18.9 ± 2.2 to 11.2 ± 1.6%, p < 0.0001) in both responders and non-responders, but non-responders remained at higher risk (15.0 ± 2.0 vs. 5.8 ± 1.6%, p < 0.0001). At baseline, plasma GDF-15 was higher in longer diabetes duration (1.19 ± 0.14 vs. 0.82 ± 0.09 ng/mL, p = 0.034), as was the QRISK (22.8 ± 2.6 vs. 15.3 ± 3.4%, p = 0.031). Leptin, GDF-15 and FGF-21 decreased whereases adiponectin increased after weight loss in responders and non-responders. However, the level of FGF-21 remained higher in non-responders (0.58 [0.28–0.71] vs. 0.25 [0.15–0.42] ng/mL, p = 0.007). QRISK change correlated with change in plasma VLDL1-TG (r = 0.489, p = 0.007). There was a positive correlation between rise in HDL cholesterol and the decrease in leptin (r = 0.57, p = 0.001), or rise in adiponectin (r = 0.58, p = 0.001) levels. In conclusion, weight loss markedly decreases cardiometabolic risk particularly when remission of diabetes is achieved. Leptin, adiponectin, GDF-15 and FGF-21 changes were related to weight loss not remission of diabetes. Normalization of 10-year cardiovascular risk and heart age is possible after substantial dietary weight loss and remission of T2DM.

Energy hormone response to fasting-induced dyslipidemia in obese and non-obese donkeys

Metabolic and endocrine disorders, such as dyslipidemia, are common in donkeys. Negative energy balance due to fasting, stressful conditions, or disease is a major trigger for fat mobilization often leading to dyslipidemia. The hormonal response to fasting has not been well characterized in donkeys. Therefore, this work aimed to study variations in insulin, glucagon, leptin, total adiponectin, ghrelin, and insulin-like growth factor-1 concentrations, insulin-to-glucagon (IGR) and glucagon-to-insulin (GIR) molar ratios, and lipid and carbohydrate parameters during a 66 h fasting period in 8 adult donkeys, and to determine differences depending on body condition.Obese donkeys developed earlier lipid mobilization (increased plasma total triglyceride and total cholesterol concentrations) compared to non-obese donkeys. Plasma glucose and leptin concentrations decreased in obese animals. After 60 h fasting, obese donkeys showed a significant increase in glucagon and decrease in leptin. GIR significantly increased, while insulin and IGR decreased in both groups. These findings support faster lipid mobilization in response to negative energy status in obese donkeys during fasting, which could be linked to greater glucagonemia and could explain the predisposition of these animals to dyslipidemia.

Low Energy Availability with and without a High-Protein Diet Suppresses Bone Formation and Increases Bone Resorption in Men: A Randomized Controlled Pilot Study.

Suppression of insulin-like growth factor 1 (IGF-1) and leptin secondary to low energy availability (LEA) may contribute to adverse effects on bone health. Whether a high-protein diet attenuates these effects has not been tested. Seven men completed three five-day conditions operationally defined as LEA (15 kcal kg fat-free mass (FFM)−1·day−1) with low protein (LEA-LP; 0.8 g protein·kg body weight (BW)−1), LEA with high protein (LEA-HP; 1.7 g protein·kg BW−1) and control (CON; 40 kcal·kg FFM−1·day−1, 1.7 g protein·kg BW−1). In all conditions, participants expended 15 kcal·kg FFM−1·day−1 during supervised cycling sessions. Serum samples were analyzed for markers of bone turnover, IGF-1 and leptin. The decrease in leptin during LEA-LP (−65.6 ± 4.3%) and LEA-HP (−54.3 ± 16.7%) was greater than during CON (−25.4 ± 11.4%; p = 0.02). Decreases in P1NP (p = 0.04) and increases in CTX-I (p = 0.04) were greater in LEA than in CON, suggesting that LEA shifted bone turnover in favour of bone resorption. No differences were found between LEA-LP and LEA-HP. Thus, five days of LEA disrupted bone turnover, but these changes were not attenuated by a high-protein diet.

Decrease in leptin mediates rat bone metabolism impairments during high-fat diet-induced catch-up growth by modulating the OPG/RANKL balance.

Due to catch-up growth (CUG), there are adverse effects on human health. However, there is little information about its influence on bone metabolism. This study aimed to investigate the effects of leptin on bone metabolism and formation during high-fat diet (HFD)-induced CUG. We randomly divided male Wistar rats (5weeks old) into four groups: control (CTL), caloric restriction and normal chow (RN), caloric restriction (4weeks), and HFD (RH), and RH + leptin antagonist (RH + LEPA). We monitored body weights, biochemical markers, and epididymal and perirenal fat in these rats. We then performed Hematoxylin and Eosin (H&E) staining to evaluate bone metabolism. We detected osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa b ligand (RANKL) by qRT-PCR and immunohistochemistry (IHC). We found that HFD increased the body weights in rats. In RN, RH, and RH + LEPA groups, major biochemical markers of bone metabolism in rat serum were significantly altered. We found that epididymal and perirenal fat tissues of RH and RH + LEPA groups were higher than those in the RN group. Severe bone formation impairment in the distal diaphysis and metaphysis of the left femora and lumbar vertebra was seen in the RH group compared to RN, which was even aggravated by a leptin antagonist. OPG in the left femora and lumbar vertebra was lower in RH than the RN group. The leptin antagonist decreased OPG during CUG in the RH group, whereas RANKL expression showed an opposite alteration. During HFD-induced CUG, bone formation was mediated by OPG and RANKL and was affected by the leptin content.

Resting-state connectivity within the brain's reward system predicts weight loss and correlates with leptin.

Weight gain is often associated with the pleasure of eating food rich in calories. This idea is based on the findings that people with obesity showed increased neural activity in the reward and motivation systems of the brain in response to food cues. Such correlations, however, overlook the possibility that obesity may be associated with a metabolic state that impacts the functioning of reward and motivation systems, which in turn could be linked to reactivity to food and eating behaviour and weight gain. In a study involving 44 female participants [14 patients with obesity, aged 20–63 years (mean: 42, SEM: 3.2 years), and 30 matched lean controls, aged 22–60 years (mean: 37, SEM: 1.8 years)], we investigated how ventromedial prefrontal cortex seed-to-voxel resting-state connectivity distinguished between lean and obese participants at baseline. We used the results of this first step of our analyses to examine whether changes in ventromedial prefrontal cortex resting-state connectivity over 8 months could formally predict weight gain or loss. It is important to note that participants with obesity underwent bariatric surgery at the beginning of our investigation period. We found that ventromedial prefrontal cortex–ventral striatum resting-state connectivity and ventromedial–dorsolateral prefrontal cortex resting-state connectivity were sensitive to obesity at baseline. However, only the ventromedial prefrontal cortex–ventral striatum resting-state connectivity predicted weight changes over time using cross-validation, out-of-sample prediction analysis. Such an out-of-sample prediction analysis uses the data of all participants of a training set to predict the actually observed data in one independent participant in the hold-out validation sample and is then repeated for all participants. In seeking to explain the reason why ventromedial pre-frontal cortex–ventral striatum resting-state connectivity as the central hub of the brain’s reward and motivational system may predict weight change over time, we linked weight loss surgery-induced changes in ventromedial prefrontal cortex–ventral striatum resting-state connectivity to surgery-induced changes in homeostatic hormone regulation. More specifically, we focussed on changes in fasting state systemic leptin, a homeostatic hormone signalling satiety, and inhibiting reward-related dopamine signalling. We found that the surgery-induced increase in ventromedial prefrontal cortex–ventral striatum resting-state connectivity was correlated with a decrease in fasting-state systemic leptin. These findings establish the first link between individual differences in brain connectivity in reward circuits in a more tonic state at rest, weight change over time and homeostatic hormone regulation.

Adiponectin/leptin ratio increases after a 12-week very low-carbohydrate, high-fat diet, and exercise training in healthy individuals: A non-randomized, parallel design study

This study aimed to investigate the effect of a 12-week very low-carbohydrate, high-fat (VLCHF) diet and exercise on biomarkers of inflammation in healthy individuals. Since the anti-inflammatory effects of a ketogenic diet have been established, we hypothesized that the VLCHF diet, along with exercise, would have an additional favorable effect on biomarkers of inflammation. Twenty-four healthy individuals were allocated to the VLCHF diet (VLCHF: N = 12, age 25.3 ± 2.0 years, body mass 66.7 ± 9.8 kg, fat mass 21.5% ± 4.9%), or habitual diet (HD: N = 12, age 23.9 ± 3.8 years, body mass 72.7 ± 15.0 kg, fat mass 23.4 ± 8.4 %) group. Biomarkers of inflammation (adiponectin, leptin, and high-sensitive interleukin-6 [hs-IL-6]) and substrate metabolism (glycated hemoglobin, fasting glucose, triacylglycerides, and cholesterol) were analyzed from blood at baseline and after 12 weeks. The adiponectin-leptin ratio significantly increased in the VLCHF group after the intervention period (ES [95% CL]: −0.90 [−0.96, −0.77], P ≤ .001, BF10 = 22.15). The adiponectin-leptin ratio changes were associated with both a significant increase in adiponectin (−0.79 [−0.91, −0.54], P ≤ .001, BF10 = 9.43) and a significant decrease in leptin (0.58 [0.19, 0.81], P = .014, BF10 = 2.70). There was moderate evidence of changes in total cholesterol (−1.15 [−2.01, −0.27], P = .010, BF10 = 5.20), and LDL cholesterol (−1.12 [−2.01, −0.21], P = .016, BF10 = 4.56) in the VLCHF group. Body weight (kg) and fat mass (%) decreased in the VLCHF group by 5.4% and 14.9%, respectively. We found that in healthy young individuals, consuming a VLCHF diet while performing regular exercise over a 12-week period produced favorable changes in body weight and fat mass along with beneficial changes in serum adiponectin and leptin concentrations. These data support the use of a VLCHF diet strategy for the primary prevention of chronic diseases associated with systemic low-grade inflammation.

Effects of High and Low Protein Diets on Inflammatory Profiles in People with Morbid Obesity: A 3-Week Intervention Study.

Nutritional interventions in morbidly obese individuals that effectively reverse a pro-inflammatory state and prevent obesity-associated medical complications are highly warranted. Our aim was to evaluate the effect of high (HP) or low (LP) protein diets on circulating immune-inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), chemerin, omentin, leptin, total adiponectin, high molecular weight adiponectin, and fetuin-A. With this aim, 18 people with morbid obesity were matched into two hypocaloric groups: HP (30E% protein, n = 8) and LP (10E% protein, n = 10) for three weeks. Biomarkers were measured pre and post intervention and linear mixed-effects models were used to investigate differences. Consuming HP or LP diets resulted in reduced CRP (HP: −2.2 ± 1.0 mg/L, LP: −2.3 ± 0.9 mg/L) and chemerin (HP: −17.9 ± 8.6 ng/mL, LP: −20.0 ± 7.4 ng/mL), with no statistically significant differences by diet arm. Participants following the LP diet showed a more pronounced decrease in leptin (−19.2 ± 6.0 ng/mL) and IL-6 (−0.4 ± 0.1 pg/mL) and an increase in total adiponectin (1.6 ± 0.6 µg/mL). Changes were also observed for the remaining biomarkers to a smaller degree by the HP than the LP hypocaloric diet, suggesting that a LP hypocaloric diet modulates a wider range of immune inflammatory biomarkers in morbidly obese individuals.

Hyperleptinemia as a contributing factor for the impairment of glucose intolerance in obesity.

Obesity has emerged as a major risk factor for insulin resistance leading to the development of type 2 diabetes (T2D). The condition is characterized by high circulating levels of the adipose-derived hormone leptin and a state of chronic low-grade inflammation. Pro-inflammatory signaling in the hypothalamus is associated with a decrease of central leptin- and insulin action leading to impaired systemic glucose tolerance. Intriguingly, leptin not only regulates body weight and glucose homeostasis but also acts as a pro-inflammatory cytokine. Here we demonstrate that increasing leptin levels (62,5µg/kg/d, PEGylated leptin) in mice fed a high-fat diet (HFD) exacerbated body weight gain and aggravated hypothalamic micro- as well as astrogliosis. In contrast, administration of a predetermined dose of a long-acting leptin antagonist (100 µg/kg/d, PESLAN) chosen to block excessive leptin signaling during diet-induced obesity (DIO) showed the opposite effect and significantly improved glucose tolerance as well as decreased the total number of microglia and astrocytes in the hypothalamus of mice fed HFD. These results suggest that high levels of leptin, such as in obesity, worsen HFD-induced micro-and astrogliosis, whereas the partial reduction of hyperleptinemia in DIO mice may have beneficial metabolic effects and improves hypothalamic gliosis.

The effects of testosterone replacement therapy in men with age-dependent hypogonadism on body composition, and serum levels of leptin, adiponectin, and C-reactive protein.

Age-related hypogonadism in men leads to abnormal body composition development and overproduction of inflammatory cytokines, and thus has atherogenic and potentially cancer promoting effects. The aim of the study was to assess the effect of agedependent testosterone deficiency replacement in men on body composition, serum leptin, adiponectin, and C-reactive protein levels. Men aged 50-65 years (56.0 ± 5.7, average ± SD), with total testosterone levels < 4 ng/mL, and clinical symptoms of hypogonadism were divided into two groups of 20 men and treated with testosterone (200 mg/two weeks intramuscularly) or placebo during 12 months. Twelve months of treatment with testosterone led to body mass index (BMI) and fat mass (FM) decrease from 26.6 ± 2.1 to 26.1 ± 1.8 kg/m², p < 0.05, and from 17.0 ± 4.4 to 15.6 ± 4.0 kg, p < 0.05, respectively. Body mass index and FM did not change in placebo-receiving subjects. Serum leptin and highly selective C-reactive protein (hsCRP) levels in testosterone group decreased from 6.2 ± 1.4 to 4.0 ± 1.2 μg/L, p < 0.05, and from 1.4 ± 1.2 to 1.0 ± 1.0 mg/L, p < 0.05 after 12 months, respectively. Adiponectin increased from 7.6 ± 2.5 μg/mL to 9.4 ± 2.8 μg/mL, p < 0.05 in the same time. In the placebo group serum leptin, adiponectin, and hsCRP levels did not change significantly. Testosterone replacement in men with age-related hypogonadism causes a decrease in body mass index, fat mass, serum leptin, and C-reactive protein levels and increases serum adiponectin levels.

Maternal Occupational Tobacco Exposure and Newborn Umbilical Cord Serum Leptin Concentration

To assess the effect of maternal occupational tobacco handling (bidi rolling) on cord serum leptin levels. We enrolled 64 neonates born to women who were bidi-rollers, and 64 small for gestational age (SGA) neonates and 57 term appropriate for gestational age (AGA) neonates born to mothers with no tobacco exposure. Cord blood leptin levels between the groups were compared. Adjusted mean difference in leptin was calculated using regression model. Cord leptin showed moderate correlation with birthweight (r=0.16; P=0.027) across the groups. Mean (SD) cord serum leptin levels (ng/mL) of study group was 19.79 (13.32), in comparison to 21.4 (13.4) of SGA (P=0.497), and 27.70 (13.96) of term AGA (P=0.002). Maternal occupational tobacco exposure contributed to significant decrease in cord leptin (adjusted mean difference (95%CI): -4.5 ng/mL (-8.82, -0.19); P=0.041). Maternal occupational tobacco exposure causes signifi-cant reduction in fetal leptin levels.