Reduced Leptin Concentrations Research Articles

Recurrent Ethanol Treatment does not Produce a Cumulative Effect on Plasma Leptin Levels in Rats

Background: Hypoleptinemia is a potent orexigenic signal. Chronic ethanol (EtOH) consumption is associated with weight gain in humans, and acute ethanol treatment leads to reductions in leptin concentrations in both fasted humans and rats. The objective of this study was to determine whether short-term recurrent ethanol treatment has a cumulative effect on plasma leptin levels in rats, and whether treatment in the fed or fasted state influences the leptin lowering effect of EtOH. We hypothesized that recurrent EtOH treatment would have a cumulative effect on leptin levels, and that these effects would be more pronounced in the fed state, when leptin levels are highest. Methods: Two separate groups of male Sprague Dawley rats were exposed to either oral or intravenous (IV) treatment with EtOH (2g/kg via oral gavage or 0.067 g/kg/min IV for 30 min; n=7/group) on three consecutive days. Each rat served as its own control and received saline treatment either 7 d prior to or 7 d following exposure to EtOH. The oral group was fasted 12-14 h (overnight) prior to treatment, while the IV group was not fasted. Plasma leptin and EtOH levels were measured each day at baseline and 3 h following EtOH treatment. Data are expressed as mean ± SEM. A two-way repeated measures ANOVA was used to test for differences in plasma leptin and EtOH levels due to treatment (saline vs. EtOH) or day (cumulative effect of treatment). Results: Post-treatment ethanol levels in the oral and IV groups (55 ± 6.9 and 45 ± 6.3 mM, respectively) were higher than saline-treated rats (p>0.001). Baseline leptin levels in the oral treatment (fasted) group were 3.4 ± 0.3 and 3.9 ± 0.2 ng/mL under saline and leptin treated conditions, respectively. There was a significant main effect of treatment but not of day in the oral group (p=0.04 and p=0.38, respectively). In the oral group, average daily change in leptin levels 3 h post treatment in saline and leptin treated rats were -0.18 ± 0.05 and -0.72 ± 0.1 ng/mL, respectively. Baseline leptin levels in the IV group (fed) were 7.8 ± 0.3 and 6.7 ± 0.1 ng/mL, in saline and leptin treated rats respectively. There was no significant main effect of treatment or day in the IV group (p=0.17 and p=0.41, respectively). In the IV group, average daily changes in leptin levels 3 h following treatment in saline and leptin treated rats were -1.7 ± 0.2 and -1.3 ± 0.3 ng/mL, respectively. Conclusion: Although we were able to replicate previous work indicating reduced leptin levels following acute EtOH treatment in fasted rats, our results do not support a cumulative leptin-lowering effect of recurrent EtOH treatment. Furthermore, IV EtOH treatment in the fed state did not have any impact on leptin levels. This suggests that the leptin-lowering effects of EtOH may either require the fasted state or may require ingestion and exposure of the GI system to EtOH. NIH R01 DK131165-01A1. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Calorie restriction-induced leptin reduction and T-lymphocyte activation in blood and adipose tissue in men with overweight and obesity.

T-Lymphocyte activation is modulated by the adipokine leptin and serum concentrations of this hormone can be reduced with short-term calorie restriction. The aim of this study was to understand whether leptin per se is important in determining levels of T-lymphocyte activation in humans, by investigating whether the reduction in leptin concentration following calorie restriction is associated with a decrease in T-Lymphocyte activation in blood and adipose tissue. Twelve men with overweight and obesity (age 35-55 years, waist circumference 95-115 cm) reduced their calorie intake by 50% for 3 consecutive days. Blood and subcutaneous adipose tissue were obtained for isolation of immune cells and cytokine analysis. CD4+ and CD8 + T-Lymphocytes were identified and characterised according to their expression of activation markers CD25 and CD69 by flow cytometry. Serum leptin was reduced by (mean ± SEM) 31 ± 16% (p < 0.001) following calorie restriction. The percentage of blood CD4 + CD25 + T-lymphocytes and level of CD25 expression on these lymphocytes were significantly reduced by 8 ± 10% (p = 0.016) and 8 ± 4% (p = 0.058), respectively. After calorie restriction, ex vivo leptin secretion from abdominal subcutaneous adipose tissue explants was not changed, and this corresponded with a lack of change in adipose tissue resident T-Lymphocyte activation. Serum leptin was reduced after calorie restriction and this was temporally associated with a reduction in activation of blood CD4 + CD25 + T-Lymphocytes. In abdominal subcutaneous adipose tissue, however, leptin secretion was unaltered, and there were no observed changes in adipose resident T-Lymphocyte activation.

Effects of Exogenous Glucocorticoid Infusion on Appetitic Center Development in Postnatal Dairy Bull Calves.

The objective of this study was to determine the effects of exogenous glucocorticoid administration on leptin concentrations and brain development markers, such as protein and hypothalamic gene expression, in dairy bull calves. Within 4 h of parturition, Holstein bulls were intravenously infused with either a low cortisol dose (LC; n = 9, 3.5 µg/kg of body weight (BW)), high cortisol dose (HC; n = 9, 7.0 µg/kg BW), or control (CON; n = 9, saline) dose, with a 2nd infusion 24 h postpartum. Jugular blood was collected prior to infusion and daily until the calves were euthanized (day 5). Cerebrospinal fluid (CSF) from the third ventricle and adipose (omental, perirenal, and mesenteric) and hypothalamic tissue were collected. The blood and CSF samples were analyzed for leptin concentrations. The data were analyzed using SAS. Serum (p = 0.013) and CSF (p = 0.005) leptin concentrations in HC- and LC-treated calves were decreased compared with CON-treated calves. Leptin protein expression was decreased (p < 0.044) in perirenal and omental adipose tissue of LC-treated calves compared with CON-treated calves. Gene abundance of brain-derived neurotrophic factor and fibroblast growth factors 1 and 2 were decreased (p < 0.006) in HC- and LC-treated calves compared with CON-treated calves. In summary, cortisol administered to dairy bull calves reduced leptin concentrations, decreased leptin protein expression in perirenal and omental adipose tissue, and altered gene expression in hypothalamic tissue.

Positive effect of leptin substitution on mood and behaviour in patients with congenital leptin deficiency.

States of starvation are characterized by reduced physical activity and social withdrawal. This has been suggested to be mediated at least in part via reduced leptin concentrations. We therefore aimed to ascertain if leptin substitution in patients with congenital leptin deficiency (CLD) can improve physical activity and mood. Seven patients with CLD were filmed prior to and after short- and long-term substitution (2-21 days; 3-4 months) in a play situation. Six independent, blinded investigators ranked each video according to specifically developed scales concerning motor activity, social interaction, emotionality, and mood with higher scores representing improvements. Short term metreleptin substitution significantly increased mean total score from 17.7 ± 4.1 to 22.6 ± 6.6 (p = 0.039), and mean scores for motor activity (4.1 ± 1.1 to 5.1 ± 1.5, p = 0.023) and social interaction (4.6 ± 1.1 to 6.2 ± 1.7, p = 0.016). After long term substitution means of all four single scales and of total score were even higher than at short-term follow-up. During a treatment pause of 3 months in two children, all four scale scores fell below substitution levels and rose again after restart. Metreleptin substitution improved indices of physical activity and psychological wellbeing in patients with CLD. This suggests that reduced leptin concentrations might be in part responsible for emotional and behavioural changes seen during starvation.

Nandrolone decanoate and resistance exercise affect body composition and energy metabolism

Our aim was to evaluate the independent and associated effects of nandrolone decanoate (DECA) and resistance exercise (REx) on central and peripheral hormones and neuropeptides related to energy balance in male rats. The experimental protocol was performed for eight weeks and comprised four groups: control (C) – exposed to vehicle 3x/wk; trained (T) – REx 5x/wk and vehicle 3x/wk; decanoate (D) – exposed to DECA (5 mg/kg) 3x/wk, and REx with DECA (TD) – submitted to REx 5x/wk and DECA (5 mg/kg) 3x/wk. Cross-sectional area analysis of the gastrocnemius muscle was higher in the T and TD groups compared to the C group. Biometrical analyses showed a decrease in body weight only in the TD compared to the C group, however, a reduction in total fat mass was observed in both the T and TD when compared to the C group. In respect of hypothalamic mRNA expression, there was an increase in prepro-orexin in the T compared to the C group. In mesenteric fat there was a decrease in leptin expression in the T and TD compared to the C group. Plasma evaluations showed reduced leptin concentrations in D, T and TD compared to C, and an increase in orexin-A in the D group compared to the C and T groups. Our data showed that REx was related to central and peripheral changes in energy metabolism, while DECA changed only peripheral components. REx associated with DECA promoted peripheral changes in energy metabolism and decreased body and fat weights.

Effects of Exogenous Glucocorticoid Administration on Appetitic Center Brain Development in Dairy Bull Calves

Abstract The objective of study was to determine the effects of exogenous cortisol on leptin concentrations and appetitic center development of perinatal dairy bull calves. Holstein bull calves (n = 27) were weighed and randomly assigned to treatments within 4 h of parturition (d0). Each calf was intravenously infused with either a low cortisol (LC; n = 9, 3.5 ug/kg of BW), high cortisol (HC; n = 9, 7.0 ug/kg of BW), or a sham infusion control (CON; n = 9, similar volume of saline). Each calf was administered a second infusion (half dose) of its respective treatment 24 h postpartum. All calves were housed similarly and fed milk replacer (28% CP, 20% fat) three times daily. Blood was collected via jugular venipuncture before infusion and from d 0–5 of age. At 5 d of age, calves were euthanized via sodium pentobarbital overdose. Cerebral-spinal fluid (CSF) from the third ventricle of the brain, hypothalamus, and adipose tissue (AT; omental, perirenal, and mesenteric) were collected. Blood and CSF samples were analyzed for leptin concentrations via a validated RIA. Adipose tissue samples were analyzed via western blotting for leptin and glucocorticoid receptor (GR) expression and normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression. Hypothalamus samples were analyzed via qRT-PCR for genes associated with neuronal growth factors and normalized to the average of two housekeeping genes. All data were analyzed via ANOVA or repeated measures analysis using appropriate models (SAS Institute Inc., Cary, NC). Serum and CSF leptin concentrations were decreased (P &amp;lt; 0.013) in HC and LC compared to CON. Leptin protein expression was decreased (P &amp;lt; 0.044) in perirenal and omental AT of LC calves compared to CON. Hypothalamic expression of BDNF, FGF1, and FGF2 were decreased (P &amp;lt; 0.006) in HC and LC compared to CON. In summary, exogenous cortisol administered to calves at birth reduced leptin concentrations and altered appetitic control center development of the brain.

Effects of Exogenous Glucocorticoid Administration on Feed Intake in Beef Cattle

Abstract Calves (n = 63) from Angus crossbred cows were weighed and randomly assigned to treatments within 4 h of parturition (d 0). Each calf was intravenously infused with either a low cortisol [LC; n = 22, 3.5 µg hydrocortisol sodium succinate/kg body weight (BW)], high cortisol (HC; n = 20, 7.0 µg/kg BW), or a sham infusion control (CON; n = 21, similar volume of saline). Each calf was administered a second infusion of its respective treatment 24 h postpartum. Blood was collected via jugular venipuncture before infusion and daily from d 0–17 of age and analyzed for leptin concentrations using a validated radioimmunoassay. Animal BW was collected every 14 d from d 0 until the end of the study. Heifers (n = 31; 367±4 d of age) and steers (n = 32; 385±4 d of age) entered a Growsafe system to measure feed intake (FI) and were allowed a 2-wk adjustment period to a commercial ration (1.27 Mcal NEm/kg and 15.8% CP and 0.45 Mcal NEg/kg and 13.8% CP, respectively; DM basis). Heifer body condition score (BCS) was collected at the beginning and end of the trial. Heifers were fed for 70 d and steers until they obtained a 12th rib back fat (BF) thickness of 1.15 cm. Data were analyzed via ANOVA or repeated measures using appropriate models of SAS. Serum leptin concentrations observed a treatment by day interaction (P = 0.0028), in which HC and LC were decreased compared to CON from d 2–17 of age. Calf birth BW and adjusted 205-d BW did not differ (P &amp;gt; 0.056) between treatments. Heifer BW gain, BCS change, and number of feed events were increased (P = 0.001) in LC compared to HC and CON. Steers did not differ between treatments (P &amp;gt; 0.080) in BW, BW gain, or BF thickness. However, LC steers observed greater daily FI (P = 0.047) and tended to have greater final BW (P = 0.080). In summary, exogenous cortisol administered to calves at parturition reduced leptin concentrations and improved FI of beef steers during a feeding trial.

60 Effects of exogenous glucocorticoid administration on leptin concentrations in perinatal dairy bull calves

Abstract Previous studies suggest a relationship between leptin and cortisol immediately postpartum is linked to improved feedlot efficiency on cattle exposed to perinatal stressors. The objective of the current study was to determine the effects of exogenous cortisol administration on circulating leptin concentrations in perinatal dairy bull calves. Within four hours of parturition, Holstein bull calves were randomly assigned to treatments and intravenously infused with low cortisol (LC; n =9, 3.5 ug/kg of cortisol), high cortisol (HC; n = 9, 7.0 ug/kg of cortisol), or a sham infusion control (CON; n = 9, similar volume of saline). Calves were housed similarly and fed milk replacer (28% CP, 20% fat) three times daily. Blood collections were performed via jugular venipuncture using Z/9mL serum collection tubes (Sarstedt, Newton, NC) from d 0 to 5 of age. Serum samples were incubated for 1 h at room temperature then overnight at 4°C, centrifuged at 1800 x g at 4°C for 20 minutes, serum decanted, and stored long term at -20°C until analysis. At 5 d of age, calves were euthanized utilizing an overdose of sodium pentobarbital (Schering-Plough Animal Health, Union, NJ) and cerebral-spinal fluid (CSF) from the third ventricle of the brain was collected and stored at -80°C until analysis. All samples were analyzed for leptin concentrations via a previously-validated radioimmunoassay. Serum leptin concentrations were analyzed via repeated measures of ANOVA and CSF leptin concentrations via the GLM procedure of SAS (SAS Institute Inc., Cary, NC, USA). Serum leptin concentrations of HC and LC were decreased (P = 0.013) compared to CON, and d 0 was decreased (P &amp;lt; 0.001) compared to all other days of age. Cerebral-spinal fluid leptin concentrations of HC and LC were decreased (P = 0.005) compared to CON. In summary, exogenous cortisol administered to perinatal dairy bull calves reduced leptin concentrations in serum and CSF.

59 Effects of exogenous glucocorticoid administration on leptin concentrations in perinatal dairy bull calves

Abstract Previous studies suggest a relationship between leptin and cortisol immediately postpartum is linked to improved feedlot efficiency on cattle exposed to perinatal stressors. The objective of the current study was to determine the effects of exogenous cortisol administration on circulating leptin concentrations in perinatal dairy bull calves. Within four hours of parturition, Holstein bull calves were randomly assigned to treatments and intravenously infused with low cortisol (LC; n = 9, 3.5 ug/kg of cortisol), high cortisol (HC; n = 9, 7.0 ug/kg of cortisol), or a sham infusion control (CON; n = 9, similar volume of saline). Calves were housed similarly and fed milk replacer (28% CP, 20% fat) three times daily. Blood collections were performed via jugular venipuncture using Z/9mL serum collection tubes (Sarstedt, Newton, NC) from d 0 to 5 of age. Serum samples were incubated for 1 h at room temperature then overnight at 4°C, centrifuged at 1800 x g at 4°C for 20 minutes, serum decanted, and stored long term at -20°C until analysis. At 5 d of age, calves were euthanized utilizing an overdose of sodium pentobarbital (Schering-Plough Animal Health, Union, NJ) and cerebral-spinal fluid (CSF) from the third ventricle of the brain was collected and stored at -80°C until analysis. All samples were analyzed for leptin concentrations via a previously-validated radioimmunoassay. Serum leptin concentrations were analyzed via repeated measures of ANOVA and CSF leptin concentrations via the GLM procedure of SAS (SAS Institute Inc., Cary, NC, USA). Serum leptin concentrations of HC and LC were decreased (P = 0.013) compared to CON, and d 0 was decreased (P &amp;lt; 0.001) compared to all other days of age. Cerebral-spinal fluid leptin concentrations of HC and LC were decreased (P = 0.005) compared to CON. In summary, exogenous cortisol administered to perinatal dairy bull calves reduced leptin concentrations in serum and CSF.

Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function.

Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. Obestatin reduced body weight and decreased serum glucose, fructosamine, and β-hydroxybutyrate levels, as well as total and low-density lipoprotein fractions of cholesterol. In addition, obestatin increased high-density lipoproteins cholesterol levels and enhanced insulin sensitivity in mice with type 2 diabetes mellitus. Moreover, obestatin diminished liver mass, hepatic triglycerides and cholesterol contents, while glycogen content was higher in livers of healthy and mice with type 2 diabetes mellitus treated with obestatin. These changes were accompanied by reduction of increased alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transpeptidase in T2DM mice with type 2 diabetes mellitus. Obestatin increased adiponectin levels and reduced leptin concentration. Obestatin influenced the expression of genes involved in lipid and carbohydrate metabolism by increasing Fabp5 and decreasing G6pc, Pepck, Fgf21 mRNA in the liver. Obestatin increased both, AKT and AMPK phosphorylation, and sirtuin 1 (SIRT1) protein levels as well as mRNA expression in the liver. Obestatin improves metabolic abnormalities in type 2 diabetes mellitus, restores hepatic lipid contents and decreases hepatic enzymes. Therefore, obestatin could potentially have a therapeutic relevance in treating of insulin resistance and metabolic dysfunctions in type 2 diabetes mellitus.

Humoral regulation of nutritional status in children

The purpose of the research was the investigation of the characteristics of insulin resistance, levels of adipokines, myokines and collagen metabolites type I in children in orphanages and social rehabilitation centers (SRC). The study involved 69 children aged 7-12 years. The first group consisted of 20 children from SRC, the second - 16 children living in orphanages, control group included 33 children (1-2 health groups) from wealthy families. The average length of stay of children in SRP was 1.0 (0.5-2.5) month, in orphanages - 38 (22-44) months. The groups were comparable in age and sex. Anthropometric indices were determined, in blood serum glucose concentration was measured by glucose oxidase method, blood serum level of insulin, cortisol, leptin, adiponectin, resistin, apelin, myostatin, collagen metabolites were determined by ELISA. Children from orphanages and SRC had significantly lower anthropometric indices in comparison with the control group. Particularly low parameters were observed in children from SRP, which in growth, body weight, chest circumference and body mass index significantly lagged behind the control group peers. The children from SRP as compared with the control group revealed higher insulin resistance index (3.33±0.49 vs 2.29±0.29, p<0.05) and cortisol level (405.21±38.21 vs 313.08±25.97 nmol/l, p>0.05). There were changes (p<0.05) in blood serum content of adipokines - reduced leptin level (5.35±1.55 vs 14.00±3.10 ng/ml) and increased apelin level (4.07±0.82 vs 2.19±0.41 ng/ml), as well as higher levels (p<0.05) of myostatin (183.95±16.3 vs 116.4±9.4 ng/ml) and C-terminal telopeptide of type I collagen (1.11±0.11 vs 0.72±0.08 ng/ml). The children in orphanages compared with the control group had lower levels of insulin (5.04±0.69 vs 11.3±1.12 μIU/ml), high insulin sensitivity - HOMA-IR was 1.01±0.16. The children in orphanages have even more pronounced reduction in leptin concentration (2.69±0.4 ng/ml), a decrease of resistin (4.99±0.32 vs 7.16±0.70 ng/ml, p<0.05), increased concentration (p<0.05) of apelin (3.53±0.67 ng/ml), myostatin (181.17±10.2 ng/ml) and C-terminal telopeptide of type I collagen (2.70±0.22 ng/ml). Features of hormone and cytokine regulation of metabolism make it particularly urgent to prevent disorders of eating behavior and to promote a healthy lifestyle among children left without parental care.

Ameliorating effects of fennel and cumin extracts on sperm quality and spermatogenic cells apoptosis by inducing weight loss and reducing leptin concentration in diet-induced obese rats.

This study was established a model of obesity to estimate the impact of fennel and cumin as anti-obesity extracts on body weight, body mass index (BMI), food consumption, leptin concentration, sperm quality and testis architecture to determine the reversibility of reproductive function of obese animals. Male rats were randomly assigned to either a normal or high-fat diet for 8weeks. Then, we divided 56 adult rats into seven groups: control (CO); obesity (OB); fennel 100 and 200mg/kg; cumin 50 and 100mg/kg; and fennel 100mg/kg plus cumin 50mg/kg. From weeks 9-16, the animals treated extracts by gavages daily. We analysed leptin concentration, sperm quality and apoptosis of testis along with evaluating changes in body weight. Body weight of animals increased 25% at week 8. However, body weight, BMI, leptin concentration and apoptosis indices of OB rats increased at the end of study. However, the relative sperm parameters decreased. Nevertheless, fennel and cumin treatment improved sperm quality, and spermatogenic cells apoptosis following weight loss. Concomitant with weight loss, leptin concentration and food consumption decreased. In conclusion, fennel and cumin as supplements may ameliorate sperm quality of obese animals following weight loss and reduction in leptin concentration.

Add-on therapy with anagliptin in Japanese patients with type-2 diabetes mellitus treated with metformin and miglitol can maintain higher concentrations of biologically active GLP-1/total GIP and a lower concentration of leptin

Metformin, α-glucosidase inhibitors (α-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients. We assessed add-on therapeutic effects of DPP-4I anagliptin in Japanese T2DM patients treated with metformin, an α-GI miglitol, or both drugs on postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of the appetite-suppressing hormone leptin. Forty-two Japanese T2DM patients with inadequately controlled disease (HbA1c: 6.5%–8.0%) treated with metformin (n=14), miglitol (n=14) or a combination of the two drugs (n=14) received additional treatment with anagliptin (100mg, p.o., b.i.d.) for 52 weeks. We assessed glycemic control, postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of leptin in those patients. Add-on therapy with anagliptin for 52 weeks improved glycemic control and increased the area under the curve of biologically active GLP-1 concentration without altering obesity indicators. Total GIP concentration at 52 weeks was reduced by add-on therapy in groups treated with miglitol compared with those treated with metformin. Add-on therapy reduced leptin concentrations. Add-on therapy with anagliptin in Japanese T2DM patients treated with metformin and miglitol for 52 weeks improved glycemic control and enhanced postprandial concentrations of active GLP-1/total GIP, and reduce the leptin concentration.

A novel heart-adipose tissue axis: Atrial natriuretic peptide and leptin interactions in man

Increased levels of leptin are common features of obesity and type 2 diabetes, reflecting leptin resistance. Reduced circulating natriuretic peptide (NP) concentrations are independently associated with type 2 diabetes and obesity, while increased natriuretic peptide levels appear to be protective. Observational studies suggest that high NP levels are associated with reduced leptin concentrations. Whether or not this is a causal relationship is unknown.

High-Fat Diets Containing Different Amounts of n3 and n6 Polyunsaturated Fatty Acids Modulate Inflammatory Cytokine Production in Mice.

Dysregulation of adipokines is a hallmark of obesity. Polyunsaturated fatty acids in fish oil may exert anti-inflammatory effects on adipose tissue mitigating the dysregulation of adipokines thereby preventing obesity. This study investigated the effects of high-fat diets containing different amounts of n3 polyunsaturated fatty acids (PUFA) on adiposity and adipokine production in mice. Mice were fed a low-fat or a high-fat diet with 16 or 45% of energy from corn oil (low n3 PUFA) in comparison with a high-fat diet containing soybean or high-oleic sunflower oil (adequate n3 PUFA) or flaxseed or fish oil (high n3 PUFA) for 11weeks. High-fat diets, regardless of types of oils, significantly increased body fat mass and body weights compared to the low-fat diet. Adipose fatty acid composition and contents reflected dietary fatty acid profiles. The high-fat fish oil diet significantly increased adiponectin and reduced leptin concentrations in both plasma and adipose tissue; it did not elevate plasma insulin concentration compared to the high-fat corn oil diet. All high-fat diets elevated concentrations of plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1) but lowered resistin concentrations in both plasma and adipose tissue. In conclusion, fish oil may be beneficial in improving insulin sensitivity by upregulation of adiponectin and downregulation of leptin production; n3 and n6 PUFA do not play a role at the dietary levels tested in reducing adiposity and production of pro-inflammatory cytokines (leptin, PAI-1, MCP-1 and resistin) and anti-inflammatory cytokine adiponectin.

The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy

To investigate the role of pro- and anti-inflammatory adipokines in the bone metabolism of non-alcoholic fatty liver disease (NAFLD) obese adolescents as well as the effects of long-term interdisciplinary therapy on metabolic-related risk factors. Forty post-puberty obese adolescents were randomly assigned into two groups: (1) NAFLD group and (2) non-NAFLD group (diagnosis by ultrasonography) and submitted to a weight loss therapy. Body composition was analyzed by air displacement plethysmography, bone mineral density (BMD) and content by dual-energy X-ray absorptiometry, blood samples were collected to measure lipid profile, hepatic enzymes, and adipokines. Leptin and adiponectin concentrations were measured by ELISA. A decrease in total body mass, BMI, body fat, visceral and subcutaneous fat, insulin concentration, HOMA-IR, total cholesterol and an increase in lean body mass were observed in both groups after therapy. It was found positive correlation between the Δ BMD and the Δ fat mass (%) (r = 0.31, P = 0.01) and negative correlations between Δ BMC with Δ HOMA-IR (r = -0.34, P = 0.02) and Δ HOMA-IR with Δ leptin (r = -0.34, P = 0.02). In addition, increased levels of adiponectin and reduction in leptin concentrations were observed in NAFLD group. In the simple regression analysis, the HOMA-IR was an independent predictor changes in BMC in total obese adolescents and in the non-NAFLD group. One year of interdisciplinary weight loss therapy for obese adolescents with or without NAFLD, could regulate bone mineral metabolism as result of an increased BMC and improved inflammatory state.

Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults

Acute and chronic sleep restrictions cause a reduction in leptin and an increase in ghrelin, both of which are associated with hunger. Given that light/dark patterns are closely tied to sleep/wake patterns, we compared, in a within-subjects study, the impact of morning light exposures (60 lux of 633-nm [red], 532-nm [green], or 475-nm [blue] lights) to dim light exposures on leptin and ghrelin concentrations after subjects experienced 5 consecutive days of both an 8-hour (baseline) and a 5-hour sleep-restricted schedule. In morning dim light, 5-hour sleep restriction significantly reduced leptin concentrations compared to the baseline, 8-hour sleep/dim-light condition (t 1,32 = 2.9; P = 0.007). Compared to the 5-hour sleep/dim-light condition, the red, green, and blue morning light exposures significantly increased leptin concentrations (t 1,32 = 5.7; P < 0.0001, t 1,32 = 3.6; P = 0.001, and t 1,32 = 3.0; P = 0.005, resp.). Morning red light and green light exposures significantly decreased ghrelin concentrations (t 1,32 = 3.3; P < 0.003 and t 1,32 = 2.2; P = 0.04, resp.), but morning blue light exposures did not. This study is the first to demonstrate that morning light can modulate leptin and ghrelin concentrations, which could have an impact on reducing hunger that accompanies sleep deprivation.

Effect of hydroxypropyl methylcellulose on obesity and glucose metabolism in a diet-induced obesity mouse model

To investigate the effect of hydroxypropyl methylcellulose (HPMC) on weight loss and metabolic disorders associated with obesity using a high-fat diet-induced obese mouse model under a high-fat diet regimen. Obese male C57BL/6J (B6) mice were fed either a high-fat (60% kcal), low-fat (10% kcal), or high-fat diet plus HPMC (4% and 8%) for 5 weeks. Body, mesenteric adipose, and liver weights were determined at the end of the study. In addition, plasma cholesterol, insulin, glucose, adiponectin, and leptin were analyzed to determine the effects of HPMC. Hepatic and fecal lipids were measured to determine the effect of HPMC on lipid absorption and metabolism. Supplementation of the high-fat diet with 4% and 8% HPMC resulted in significant weight loss in obese B6 mice. Furthermore, significant decreases were seen in adipose (30%-40%), liver weights (15%-26%), and concentrations of plasma cholesterol (13%-20%) and hepatic lipids (13%-36%). Supplementation with 8% HPMC led to significant improvements in glucose homeostasis and leptin concentrations. Reductions in plasma cholesterol, glucose, and insulin levels were strongly correlated with reduced leptin concentrations. Moreover, increases in fecal secretion of total bile acids, sterols, and fats indicated altered fat absorption when HPMC was incorporated in the diet. The data indicate that HPMC not only reduces body weight, but also normalizes the metabolic abnormalities associated with obesity and suggest that the effects of HPMC on glucose and lipid homeostasis in B6 mice are mediated by improvements in leptin sensitivity resulting from reduced fat absorption.

Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program

It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic improvements during weight loss is uncertain. The objective was to prospectively examine associations between plasma leptin, body fat, and weight and metabolic risk factors in obese children during weight loss. In obese children and adolescents [n = 203; mean age: 14.1 y, >98th body mass index (BMI) percentile for age and sex] participating in a 2-mo inpatient weight-loss program, we measured changes in body composition (by dual-energy X-ray absorptiometry), plasma leptin, insulin, and lipids. After discharge, anthropometric measures and plasma leptin were remeasured at 6 (n = 139) and 12 (n = 100) mo. During the 2-mo program, mean (±SD) weight and fat loss were 13.9 ± 4.0 kg and 9.2 ± 2.5 kg, respectively; and mean plasma leptin decreased by 76%. Weight and fat loss were sustained, and no significant differences in BMI-SD score (SDS) or body composition were found between 12 and 2 mo. Baseline leptin was a negative predictor for percentage fat loss at 2, 6, and 12 mo (P < 0.05). The percentage change in leptin during the 2-mo intervention positively correlated with the relative change in fasting insulin, the relative change in LDL cholesterol at 2 mo, percentage fat loss, and change in BMI-SDS at 2 and 6 mo (P < 0.02). Even in obese children with strongly elevated baseline leptin, large leptin reductions that predict short- and long-term loss of body fat and improvements in lipids and insulin sensitivity can be achieved. Thus, increased plasma leptin in obese children may not necessarily reflect leptin resistance; many children appear to remain leptin sensitive at this age.

Phenotypic and genetic variation in leptin as determinants of weight regain

Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention. In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the 'weight loss phase' (0-6 months) and the 'weight maintenance/regain phase' (7-24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP). Mean weight reduction was -5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7-24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0- to 6-month weight loss (β = -0.222, P-value = 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (β = 0.505, P-value < 0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (β = -0.131, P-value < 0.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin (+3.4% (95% confidence interval 2.1-4.8)) as compared with those in the lowest combined tertiles (+0.2% (95% confidence interval -1.1 to 1.4)); P-value < 0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P = 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%. Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with greater weight loss in the short term, plasma leptin reduction, combined with the degree of initial weight loss and with genetic variations in the LEP gene, constitutes a significant predictor of subsequent long-term weight regain.