scholarly journals Leptin resistance: unsolved diagnostic issues

2018 ◽  
Vol 64 (1) ◽  
pp. 62-66
Author(s):  
Daria A. Borodkina ◽  
Olga V. Gruzdeva ◽  
Olga E. Akbasheva ◽  
Ekaterina V. Belik ◽  
Elena I. Palicheva ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Skeletal Muscles ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Fatty Tissue ◽  
Leptin Receptors ◽  
Secretion Regulation ◽  
Tissue Sensitivity

Leptin and its receptors are key regulators of body weight and energy homeostasis. A decrease in tissue sensitivity to leptin leads to the development of obesity, insulin resistance, dyslipidemia, etc. Currently, the phenomenon of leptin resistance is explained by a number of mechanisms, including impairment of gene structure, leptin transport through the blood-brain barrier, and leptin receptor signaling. However, it is not known, a decrease in the number of receptors of which area leads to the development of leptin resistance. No relationship has been found between the basal leptin level in obesity and expression of leptin receptors in the skeletal muscles. It is also important to investigate the contribution of fatty tissue of different localization to leptin secretion regulation and activity of its receptors. The term «leptin resistence» reflects a complex pathophysiological phenomenon with broad perspectives for study. In this review, we analyze methods of diagnosing leptin resistance.

scholarly journals Leptin resistance: unsolved diagnostic issues

2018 ◽  
Vol 64 (1) ◽  
pp. 62-66
Author(s):  
Daria A. Borodkina ◽  
Olga V. Gruzdeva ◽  
Olga E. Akbasheva ◽  
Ekaterina V. Belik ◽  
Elena I. Palicheva ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Skeletal Muscles ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Fatty Tissue ◽  
Leptin Receptors ◽  
Secretion Regulation ◽  
Tissue Sensitivity

Leptin and its receptors are key regulators of body weight and energy homeostasis. A decrease in tissue sensitivity to leptin leads to the development of obesity, insulin resistance, dyslipidemia, etc. Currently, the phenomenon of leptin resistance is explained by a number of mechanisms, including impairment of gene structure, leptin transport through the blood-brain barrier, and leptin receptor signaling. However, it is not known, a decrease in the number of receptors of which area leads to the development of leptin resistance. No relationship has been found between the basal leptin level in obesity and expression of leptin receptors in the skeletal muscles. It is also important to investigate the contribution of fatty tissue of different localization to leptin secretion regulation and activity of its receptors. The term «leptin resistence» reflects a complex pathophysiological phenomenon with broad perspectives for study. In this review, we analyze methods of diagnosing leptin resistance.

scholarly journals FRUCTOSE ALTERS THE EXPRESSION OF TYPE B LEPTIN RECEPTOR IN HYPHOTALAMUS AND INTESTINUM OF Rattus Novergicus

2018 ◽  
Vol 2 (2) ◽  
pp. 26
Author(s):  
Ermin Rachmawati ◽  
Risma Aprinda Kristanti ◽  
Nurlaili Susanti
Keyword(s):  
Insulin Resistance ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Intestinal Cell ◽  
Control Group ◽  
Type B ◽  
Leptin Receptors ◽  
Induce Insulin Resistance ◽  
Group 2 ◽  
Levene Test

<p><strong>Background</strong>: Several epidemiological data’s reported significant correlation between fructose consumption and diabetes mellitus type 2 by inducing insulin resistance. Leptin resistance induced by fructose was proposed as one novel mechanism that induce insulin resistance but the exact mechanism remains unclear.  We hypothesize that fructose diminish the type b leptin receptors in hypothalamus and intestine.</p><p><strong>Aim</strong>: This study was aimed to elucidate fructose effect on the expression of leptin receptor type b in hypothalamus and intestine of Rattus novergicus.</p><p><strong>Method</strong>: twenty eight rats were used and divided into 4 groups: Group 1 was control, group 2 was given fructose 10%, group 3 was given fructose 30% and group 4 was given fructose 55% for 2 months. At the end of treatment, the animal were sacrificed and then the hypothalamus and intestine were collected. The expression of type b leptin receptor were measured by immunohistochemistry technique with primary antibody from <em>Bioss antibodies type</em> <em>Leptin receptor polyclonal antibody bs-0109R using </em>Staining kit <em>Skytec Laboratories and DAB chromogen. </em>A positive expression can be seen as a brown colour in cell cytoplasm and counted in 100 cell. The expression then analysed using SPSS 18 with anova one way tes (p&lt;0,05) followed by post hoc test after the data showed normality and homogeneity using Saphiro wilk and Levene test (p&gt;0,05).</p><p><strong>Result</strong>: There was significant differences in type b leptin receptors found in hypothalamus between each group (p&lt;0.05). The significant differences also could be seen in the expression between control and group fructose 30 and 50% in intestinal cell (p&lt;0.05).</p><p><strong>Conclusion</strong>: the consumption of Fructose 55% for 2 months attenuates the expression of type b leptin receptors in hypothalamus and intestine of <em>R</em><em>at novergicus</em>.</p><p> </p>

scholarly journals Recent advances in understanding leptin signaling and leptin resistance

2009 ◽  
Vol 297 (6) ◽  
pp. E1247-E1259 ◽  
Author(s):  
David L. Morris ◽  
Liangyou Rui
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Risk Factor ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Leptin Signaling ◽  
Long Form ◽  
The Brain ◽  
Primary Risk Factor

The brain controls energy homeostasis and body weight by integrating various metabolic signals. Leptin, an adipose-derived hormone, conveys critical information about peripheral energy storage and availability to the brain. Leptin decreases body weight by both suppressing appetite and promoting energy expenditure. Leptin directly targets hypothalamic neurons, including AgRP and POMC neurons. These leptin-responsive neurons widely connect to other neurons in the brain, forming a sophisticated neurocircuitry that controls energy intake and expenditure. The anorexigenic actions of leptin are mediated by LEPRb, the long form of the leptin receptor, in the hypothalamus. LEPRb activates both JAK2-dependent and -independent pathways, including the STAT3, PI 3-kinase, MAPK, AMPK, and mTOR pathways. These pathways act coordinately to form a network that fully mediates leptin response. LEPRb signaling is regulated by both positive (e.g., SH2B1) and negative (e.g., SOCS3 and PTP1B) regulators and by endoplasmic reticulum stress. Leptin resistance, a primary risk factor for obesity, likely results from impairment in leptin transport, LEPRb signaling, and/or the neurocircuitry of energy balance.

scholarly journals Role of neonatal hyperleptinaemia on serum adiponectin and suppressor of cytokine signalling-3 expression in young rats

2008 ◽  
Vol 101 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Magna Cottini Fonseca Passos ◽  
Fabiane Pereira Toste ◽  
Sheila Cristina Potente Dutra ◽  
Paula Affonso Trotta ◽  
Fernanda Pereira Toste ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Serum Insulin ◽  
Leptin Resistance ◽  
Serum Adiponectin ◽  
Lower Serum ◽  
Serum Adiponectin Concentration

Previously we had shown that neonatal leptin treatment programmes for both hyperleptinaemia and hyperinsulinaemia, which lead to leptin resistance and low expression of the hypothalamic leptin receptor (OB-Rb) of rats aged 150 d. Here we investigated in young post-weaned rats (age 30 d) if leptin treatment during lactation induces leptin and insulin resistance and if those changes are accompanied by changes in the suppressor of cytokine signalling-3 (SOCS-3) expression and serum adiponectin concentration. After delivery, the pups were divided into two groups: (1) a leptin group (Lep) that were injected with leptin daily (8 μg/100 g body weight subcutaneously) for the first 10 d of lactation; (2) a control (C) group, receiving saline. After weaning (day 21), body weight was monitored until the animals were age 30 d. They were tested for food intake in response to either leptin (0·5 mg/kg body weight intraperitoneally) (CL, LepL) or saline (CSal, LepSal) when they were aged 30 d. The CL group showed lower food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group had hyperleptinaemia (five-fold), hyperinsulinaemia (+42·5 %) and lower levels of serum adiponectin ( − 43·2 %). The hypothalamic expression of OB-Rb was lower ( − 22 %) and SOCS-3 was higher (+52·8 %) in the Lep group. We conclude that neonatal leptin treatment programmes for leptin resistance as soon as 30 d and suggests that SOCS-3 appears to be of particular importance in this event. In the Lep group, the lower serum adiponectin levels were accompanied by higher serum insulin, indicating a probable insulin resistance.

scholarly journals Neurochemical Characterization of Body Weight-Regulating Leptin Receptor Neurons in the Nucleus of the Solitary Tract

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4600-4607 ◽  
Author(s):  
Alastair S. Garfield ◽  
Christa Patterson ◽  
Susanne Skora ◽  
Fiona M. Gribble ◽  
Frank Reimann ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Fluorescent Protein ◽  
Solitary Tract ◽  
Leptin Receptors ◽  
Receptor Neurons ◽  
Green Fluorescent ◽  
Oxide Synthase ◽  
Prolactin Releasing Peptide

Abstract The action of peripherally released leptin at long-form leptin receptors (LepRb) within the brain represents a fundamental axis in the regulation of energy homeostasis and body weight. Efforts to delineate the neuronal mediators of leptin action have recently focused on extrahypothalamic populations and have revealed that leptin action within the nucleus of the solitary tract (NTS) is critical for normal appetite and body weight regulation. To elucidate the neuronal circuits that mediate leptin action within the NTS, we employed multiple transgenic reporter lines to characterize the neurochemical identity of LepRb-expressing NTS neurons. LepRb expression was not detected in energy balance-associated NTS neurons that express cocaine- and amphetamine-regulated transcript, brain-derived neurotrophic factor, neuropeptide Y, nesfatin, catecholamines, γ-aminobutyric acid, prolactin-releasing peptide, or nitric oxide synthase. The population of LepRb-expressing NTS neurons was comprised of subpopulations marked by a proopiomelanocortin-enhanced green fluorescent protein (EGFP) transgene and distinct populations that express proglucagon and/or cholecystokinin. The significance of leptin action on these three populations of NTS neurons was assessed in leptin-deficient Ob/Ob mice, revealing increased NTS proglucagon and cholecystokinin, but not proopiomelanocortin, expression. These data provide new insight into the appetitive brainstem circuits engaged by leptin.

scholarly journals Neonatal leptin treatment programmes leptin hypothalamic resistance and intermediary metabolic parameters in adult rat

2006 ◽  
Vol 95 (4) ◽  
pp. 830-837 ◽  
Author(s):  
Fabiane Pereira Toste ◽  
Egberto Gaspar de Moura ◽  
Patrícia Cristina Lisboa ◽  
Aline Teixeira Fagundes ◽  
Elaine de Oliveira ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
The Body ◽  
Leptin Resistance ◽  
Control Group ◽  
Adult Rats ◽  
Leptin Receptors ◽  
Adult Rat ◽  
Anorectic Effect

We previously showed that neonatal leptin treatment programmes higher body weight and food intake in adult rats. Here we investigate whether leptin treatment during lactation affects the anorectic effect of leptin on adult rats and their hypothalamic leptin receptors (OB-Rb) and whether those changes could have consequences on intermediary metabolism. When the offspring were born, pups were divided into two groups: the Lep group, injected daily with leptin (8μg/100g body weight, subcutaneously) for the first 10d of lactation, and the control group, injected daily with saline. After weaning (day 21), body weight and food intake were monitored until the rats were 150d old. Food intake was higher in the Lep group (approximately 14%, p<0·05) from day 133 onwards, and body weight was higher (approximately 10%, p<0·05) from day 69 onwards, compared with the control group. At 150d of age, the rats were tested for food intake in response to either leptin (05mg/kg body weight intraperitoneally; groups CL and LepL) or saline (groups CSal and LepSal). The CL group showed a decrease in food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group demonstrated a decrease in OB-Rb expression (−40% p<0·05), hyperleptinaemia (+78%, p<0·05), hyperinsulinaemia (+100%, p<0·02), hypertriacylglycerolaemia (+17%, p<0·05) and a higher protein content in the body (+16%, p<0·05) without changes in fat mass and glycaemia. We conclude that neonatal leptin treatment programmes both hyperleptinaemia and hyperinsulinaemia in adulthood, which leads to leptin resistance by reducing the expression of the hypothalamic leptin receptor.

scholarly journals Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1598-1610 ◽  
Author(s):  
Maria M. Glavas ◽  
Melissa A. Kirigiti ◽  
Xiao Q. Xiao ◽  
Pablo J. Enriori ◽  
Sarah K. Fisher ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
Leptin Resistance ◽  
Signal Transducer ◽  
High Fat ◽  
Insulin Tolerance ◽  
Obesity And Diabetes ◽  
Transcription 3

Childhood obesity increases the risk of adult obesity and diabetes, suggesting that early overnutrition permanently programs altered energy and glucose homeostasis. In the present studies, we used a mouse model to investigate whether early overnutrition increases susceptibility to obesity and insulin resistance in response to a high-fat diet (HFD). Litters from Swiss Webster dams were culled to three [chronic postnatal overnutrition (CPO)] or 10 (control) pups and then weaned onto standard chow at postnatal day (P) 23. At 6 wk of age, a subset of mice was placed on HFD, and glucose and insulin tolerance were examined at 16–17 wk of age. Leptin sensitivity was determined by hypothalamic phosphorylated signal transducer and activator of transcription-3 immunoreactivity at P16 and adulthood after ip leptin. CPO mice exhibited accelerated body weight gain and hyperleptinemia during the preweaning period but only a slightly heavier body weight and normal glucose tolerance in adulthood on standard chow diet. Importantly, CPO mice exhibited significant leptin resistance in the arcuate nucleus, demonstrated by reduced activation of phospho-signal transducer and activator of transcription-3, as early as P16 and throughout life, despite normalized leptin levels. In response to HFD, CPO but not control mice displayed insulin resistance in response to an insulin tolerance test. In conclusion, CPO mice exhibited early and persistent leptin resistance in the arcuate nucleus and, in response to HFD, rapid development of obesity and insulin resistance. These studies suggest that early overnutrition can permanently alter energy homeostasis and significantly increase susceptibility to obesity and insulin resistance.

scholarly journals Changes in Expression of the Genes for the Leptin Signaling in Hypothalamic-Pituitary Selected Areas and Endocrine Responses to Long-Term Manipulation in Body Weight and Resistin in Ewes

2020 ◽  
Vol 21 (12) ◽  
pp. 4238
Author(s):  
Dorota Anna Zieba ◽  
Weronika Biernat ◽  
Malgorzata Szczesna ◽  
Katarzyna Kirsz ◽  
Justyna Barć ◽  
...  
Keyword(s):  
Body Weight ◽  
Leptin Receptor ◽  
Fat Body ◽  
Density Lipoprotein ◽  
Reproductive Hormones ◽  
Leptin Resistance ◽  
Nonesterified Fatty Acid ◽  
Cytokine Signaling ◽  
Leptin Signaling

Both long-term undernutrition and overnutrition disturb metabolic balance, which is mediated partially by the action of two adipokines, leptin and resistin (RSTN). In this study, we manipulated the diet of ewes to produce either a thin (lean) or fat (fat) body condition and investigated how RSTN affects endocrine and metabolic status under different leptin concentrations. Twenty ewes were distributed into four groups (n = 5): the lean and fat groups were administered with saline (Lean and Fat), while the Lean-R (Lean-Resistin treated) and Fat-R (Fat-Resistin treated) groups received recombinant bovine resistin. Plasma was assayed for LH, FSH, PRL, RSTN, leptin, GH, glucose, insulin, total cholesterol, nonesterified fatty acid (NEFA), high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Expression levels of a suppressor of cytokine signaling (SOCS-3) and the long form of the leptin receptor (LRb) were determined in selected brain regions, such as the anterior pituitary, hypothalamic arcuate nucleus, preoptic area and ventro- and dorsomedial nuclei. The results indicate long-term alterations in body weight affect RSTN-mediated effects on metabolic and reproductive hormones concentrations and the expression of leptin signaling components: LRb and SOCS-3. This may be an adaptive mechanism to long-term changes in adiposity during the state of long-day leptin resistance.

scholarly journals Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications

2019 ◽  
Vol 20 (9) ◽  
pp. 2109 ◽  
Author(s):  
Arulkumar Nagappan ◽  
Jooyeon Shin ◽  
Myeong Ho Jung
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Hepatic Steatosis ◽  
Cannabinoid Receptor ◽  
Inflammatory Responses ◽  
Hepatic Insulin Resistance ◽  
Leptin Resistance ◽  
Peripheral Tissues

Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses. Additionally, blocking peripheral CB1R improves insulin sensitivity and glucose metabolism and also reduces hepatic steatosis and body weight in obese mice. Thus, targeting EC receptors, especially CB1R, may provide a potential therapeutic strategy against obesity and insulin resistance. There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance. Recently, the use of CB1R antagonists was suspended due to adverse central effects, and this caused a major setback in the development of CB1R antagonists. Recent studies, however, have focused on development of antagonists lacking adverse effects. In this review, we detail the important role of CB1R in hepatic insulin resistance and the possible underlying mechanisms, and the therapeutic potential of CB1R targeting is also discussed.

scholarly journals Collective and Individual Functions of Leptin Receptor Modulated Neurons Controlling Metabolism and Ingestion

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1773-1785 ◽  
Author(s):  
Esther van de Wall ◽  
Rebecca Leshan ◽  
Allison W. Xu ◽  
Nina Balthasar ◽  
Roberto Coppari ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Normal Glucose Tolerance ◽  
Adult Mice ◽  
Normal Glucose ◽  
High Doses ◽  
Agouti Gene

Two known types of leptin-responsive neurons reside within the arcuate nucleus: the agouti gene-related peptide (AgRP)/neuropeptide Y (NPY) neuron and the proopiomelanocortin (POMC) neuron. By deleting the leptin receptor gene (Lepr) specifically in AgRP/NPY and/or POMC neurons of mice, we examined the several and combined contributions of these neurons to leptin action. Body weight and adiposity were increased by Lepr deletion from AgRP and POMC neurons individually, and simultaneous deletion in both neurons (A+P LEPR-KO mice) further increased these measures. Young (periweaning) A+P LEPR-KO mice exhibit hyperphagia and decreased energy expenditure, with increased weight gain, oxidative sparing of triglycerides, and increased fat accumulation. Interestingly, however, many of these abnormalities were attenuated in adult animals, and high doses of leptin partially suppress food intake in the A+P LEPR-KO mice. Although mildly hyperinsulinemic, the A+P LEPR-KO mice displayed normal glucose tolerance and fertility. Thus, AgRP/NPY and POMC neurons each play mandatory roles in aspects of leptin-regulated energy homeostasis, high leptin levels in adult mice mitigate the importance of leptin-responsiveness in these neurons for components of energy balance, suggesting the presence of other leptin-regulated pathways that partially compensate for the lack of leptin action on the POMC and AgRP/NPY neurons.

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