Serum Leptin Levels In Mice Research Articles

Effects of salmon cartilage proteoglycan on obesity in mice fed with a high-fat diet.

This study investigated the effects of salmon nasal cartilage proteoglycan (PG), which shows anti‐inflammatory properties, on obesity induced by high‐fat diet (HFD) in a mouse model. Mice were fed either a HFD or normal diet (ND), with or without PG, for 8–12 weeks. After 12 weeks, the body weight of mice fed with PG‐free HFD was 54.08 ± 4.67 g, whereas that of mice fed with HFD containing PG was 41.83 ± 4.97 g. The results suggest that the increase in body weight was attenuated in mice fed with HFD containing PG. This effect was not observed in mice fed with ND. The PG administration suppressed the elevation of serum lipids (the level of serum lipids ranged between 54% and 69% compared to 100% in mice fed with PG‐free HFD) and the upregulated mRNA expression of sterol regulatory element‐binding protein‐1c (SREBP‐1c), which is a transcription factor that acts as a master regulator of lipogenic gene expression in the liver (the expression level was 77.5% compared to 100% in mice fed with PG‐free HFD). High leptin levels in mice fed with PG‐free HFD were observed during fasting (average at 14,376 ng/ml), and they did not increase after refeeding (average of 14,263 ng/ml), whereas serum leptin levels in mice fed with HFD containing PG were low during fasting (average of 6481 ng/ml) and increased after refeeding (average 13,382 ng/ml). These results suggest that PG feeding has an anti‐obesity effect and that the regulation of SREBP‐1c and leptin secretion play a role in this effect.

Chitosan attenuates obesity by modifying the intestinal microbiota and increasing serum leptin levels in mice

Abstract Chitosan has been applied as a food additive due to its prebiotic functions, while the relationship between changes in the intestinal microbiota caused by chitosan and weight loss remains unclear. This study confirmed the weight control effect of chitosan in the context of high-fat diet consumption. Interestingly, chitosan increased the serum leptin level in the high-fat diet groups and increased the oral glucose tolerance in the low-fat diet groups. Chitosan reduced the chronic inflammation caused by high-fat diet consumption. Moreover, the intestinal microbiome was influenced by the chitosan intervention as the feeding time increased. Chitosan supplementation increased the anti-obesity-related species, such as Coprobacillus cateniformis and Clostridium leptum, and significantly decreased Clostridium lactatifermentans and Clostridium cocleatum. Spearman correlation analysis showed that Coprobacillus cateniformis and Clostridium leptum were positively correlated with serum leptin. This study suggests that the prebiotic effect of chitosan is closely related to the modification of the gut microbiota.

Neuregulin 1 affects leptin levels, food intake and weight gain in normal-weight, but not obese, db/db mice

AimStudies in vitro have highlighted the potential involvement of neuregulin 1 (NRG1) in the regulation of energy metabolism. This effect has also been suggested in vivo, as intracerebroventricular injection of NRG1 reduces food intakes and weight gain in rodents. Thus, it was hypothesised that NRG1 might affect serum leptin levels in mice. MethodsWeight, food intakes, energy expenditure, spontaneous physical activity and serum leptin levels were evaluated in normal-weight C57BL/6JRJ mice following intraperitoneal administration of NRG1 (50μg/kg, three times/week) or saline for 8 weeks. Based on the results of this first experiment, leptin-resistant obese db/db mice were then given NRG1 for 8 weeks. ResultsLeptin serum concentrations were six times higher in C57BL/6JRJ mice treated with NRG1 than in the animals given saline. NRG1 treatment also reduced weight gain by 10% and food intakes by 15% compared with saline treatment, while energy expenditure remained unchanged. In db/db mice, serum leptin concentrations, weight gain, food intakes, energy expenditure and spontaneous physical activity were not altered by NRG1 treatment. ConclusionThe decrease in food intakes and weight gain associated with NRG1 treatment in C57BL/6JRJ mice may be partly explained by increased leptin levels, whereas db/db mice were not affected by the treatment, suggesting resistance to NRG1 in this pathological state.

A Pegylated Leptin Antagonist Ameliorates CKD-Associated Cachexia in Mice

Elevated serum leptin levels correlate with inflammation and predict changes in lean body mass in patients with CKD, and activation of the melanocortin system by leptin signaling mediates the pathophysiology of CKD-associated cachexia. We tested whether treatment with a pegylated leptin receptor antagonist (PLA) attenuates cachexia in mice with CKD. CKD and Sham mice received vehicle or PLA (2 or 7 mg/kg per day). At these doses, PLA did not influence serum leptin levels in mice. Treatment with 7 mg/kg per day PLA stimulated appetite and weight gain, improved lean mass and muscle function, reduced energy expenditure, and normalized the levels of hepatic TNF-α and IL-6 mRNA in mice with CKD. Furthermore, treatment with 7 mg/kg per day PLA attenuated the CKD-associated increase in the transcriptional and protein abundance of uncoupling proteins that mediates thermogenesis, and it normalized the molecular signatures of processes associated with muscle wasting in CKD, including proteolysis, myogenesis and muscle regeneration, and expression of proinflammatory muscle cytokines, such as IL-1α, -1β, and -6 and TNF-α. Our results suggest that leptin antagonism may represent a viable therapeutic strategy for cachexia in CKD.

Role of leptin and tumor necrosis factor- (tnf-) in mechanisms of anorexia during endotoxin infection in mice

Background: Anorexia and loss of body weight are hallmark of infection. The actualmechanisms by which infection induces anorexia are still unknown. Several proinflammatorycytokines, most notably tumor necrotic factor- (TNF-), known toinitiate and modulate the host response to infection have been shown to induceanorexia and weight loss in healthy animals. Leptin is a protein hormone produced byadipose tissue. It is considered to be a satiety factor as it decreases food intake andincreases energy expenditure. Administration of bacterial endotoxin (LPS) or TNF-induced increase in serum leptin levels, and leptin has been shown to act in anendocrine fashion to decrease food intake and body weight. This suggests that leptinmay be one of the mechanisms by which anorexia is induced during infection. Thepresent study aimed to investigate the effect of endotoxin (LPS) and TNF-, on foodintake, body weight and serum leptin levels in mice. Also, to explain the differentpossible mechanisms which can cause anorexia during infection and if leptin isinvolved in these mechanisms. Methods: The study included 36 adult female micewhich were divided into 6 groups, 6 mice each. Group I: “control group”, receivedsingle intraperitoneal (i.p) injection of normal saline. Group II, III, IV and V: “LPStreated groups”, received a single i.p. injection of different doses of LPS, (0.1g, 1g,10g and 100g/100g. body weight respectively). Group VI: “TNF- treated group”,injected i.p. with TNF- in a dose of 17g/100g BW. Food intake and body weightwere measured over the next 18, 42, 66 and 90 h for animals of control and LPStreated groups. Food intake by TNF- injected group was measured 18 h afterinjection. Blood sample from each mouse of all studied animal groups was collected18 h after different injections, then serum leptin level was assessed using mouse leptinELISA kits. Results: The study showed a significant (p is<0.001), dose dependentdecrease in food intake and body weight 18 h after injection in all LPS injectedgroups (except for group II which showed a non significant decrease) when comparedwith that of control group. Gradual recovery of food intake and body weight gainingover the next 3 days occurred in low doses treated groups (groups II & III), while asmice treated with large doses, (group VI & V), showed no food intake nor weight gainover the subsequent 42 h. Thereafter, group IV began to increase their food intakeand body weight till the end of the study, whereas group V remained anorectic andlosing weight till the end of the study. TNF- injected group showed a significantdecrease in food intake, ( p is<0.001) as compared to the control one, that decreasein food intake after TNF- injection is nearly similar to that induced by LPS injection even in high doses injected groups (groups III & IV). Serum leptin levelsshowed significant increase 18 h after LPS and TNF- injection in all injected groupsin a dose related manner, compared to that of the control group. The highest dose ofLPS injection to group V “100 g / 100 g BW” showed increased serum leptin levelsnearly 4 folds to that level of control group. The increase in serum leptin levels afterTNF- injection, did not reach the same levels of increase as after LPS injectionsspecially for the high doses of LPS “groups IV and V”. Conclusion: The presentstudy showed that both of LPS and TNF- can induce anorexia and increased leptinlevel. The decrease in food intake is inversely proportional to the increase in serumleptin. These data suggest a role for leptin in anorexia during LPS infection. Also, thestudy revealed some possible mechanisms for anorexia during infection through thecooperation between immune activation mediators (cytokines) and some hormonalchanges which can induce different host’s immune and metabolic response duringinfection. As anorexia plays a critical role in chronic inflammatory diseases, it ispossible that development of leptin antagonists may play a useful role in decreasinganorexia and wasting of chronic infections such as AIDS.

Involvement of Leptin in Hypophagia Induced by the Serotonin Precursor 5-Hydroxytryptophan (5-HTP) in Mice

We previously demonstrated that a serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) increases serum leptin levels in mice. It was reported that administration of 5-HTP elicits hypophagia in rodents and humans. In the present study, we examined involvement of leptin in 5-HTP-elicited decreases in the milk intake of fasted mice. Serum leptin levels increased with increases in milk intake in mice, while 5-HTP strongly decreased milk intake in fasted mice compared to that in the control group. Serum leptin levels in fasted mice treated with 5-HTP were similar to those control mice after milk intake. As leptin is a powerful anorectic signal, 5-HTP-induced anorexia may be mediated by facilitation of leptin secretion.

Serum leptin levels after central and systemic injection of a serotonin precursor, 5-hydroxytryptophan, in mice

Effects of peripheral and central injections of a serotonin (5-hydroxytryptamine, 5-HT) precursor, 5-hydroxytryptophan (5-HTP), on serum leptin levels were studied in mice. Intracerebroventricular (i.c.v.) injection of 5-HTP or 5-HT did not increase serum leptin levels, although the peripheral injection of 5-HTP elicited an apparent hyperleptinemia. The elevation of serum leptin levels in mice induced by the peripheral injection of 5-HTP was inhibited by pretreatment with the peripheral aromatic amino acid decarboxylase inhibitor, benserazide. Furthermore, the peripheral injection of 5-HT increased serum leptin levels. These results suggest that the hyperleptinemia following systemic injection of 5-HTP is elicited by 5-HT formed in the peripheral system.

The serotonin precursor 5-hydroxytryptophan elevates serum leptin levels in mice

The effects of a serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) on serum leptin levels were investigated in mice. 5-HTP dose dependently increased serum leptin levels in mice. Pretreatment of the peripheral aromatic amino acid decarboxylase inhibitor carbidopa suppressed 5-HTP-induced hyperleptinemia. These results suggest that the secretion of leptin may be modified by serotonergic mechanisms.