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Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders.
Smitka, K, Prochazkova, P, Roubalova, R, Dvorak, J, Papezova, H, Hill, M, Pokorny, J, Kittnar, O, Bilej, M, Tlaskalova-Hogenova, H
Frontiers in endocrinology. 2021;:613983
Abstract
The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.
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2.
Sex Differences in Adipose Tissue Function.
Gavin, KM, Bessesen, DH
Endocrinology and metabolism clinics of North America. 2020;(2):215-228
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Abstract
Regional adipose tissue distribution differs between men and women. Differences in the accumulation of adipose tissue as well as the regulation of secretion of a number of products from adipose tissue are under the control of sex steroids, which act through a wide variety of mechanisms, both direct and indirect, to tailor metabolism to the unique needs of each sex. A fuller understanding of sex-based differences in adipose tissue function may help with tailored strategies for disease prevention and treatment and provide insights into fundamental differences in the processes that regulate nutrient homeostasis and body weight.
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Recent advances in understanding the role of leptin in energy homeostasis.
Münzberg, H, Singh, P, Heymsfield, SB, Yu, S, Morrison, CD
F1000Research. 2020
Abstract
The hormone leptin plays a critical role in energy homeostasis, although our overall understanding of acutely changing leptin levels still needs improvement. Several developments allow a fresh look at recent and early data on leptin action. This review highlights select recent publications that are relevant for understanding the role played by dynamic changes in circulating leptin levels. We further discuss the relevance for our current understanding of leptin signaling in central neuronal feeding and energy expenditure circuits and highlight cohesive and discrepant findings that need to be addressed in future studies to understand how leptin couples with physiological adaptations of food intake and energy expenditure.
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Temporal Leptin to Determine Cardiovascular and Metabolic Fate throughout the Life.
Kim, JG, Lee, BJ, Jeong, JK
Nutrients. 2020;(11)
Abstract
Leptin links peripheral adiposity and the central nervous system (CNS) to regulate cardiometabolic physiology. Within the CNS, leptin receptor-expressing cells are a counterpart to circulating leptin, and leptin receptor-mediated neural networks modulate the output of neuroendocrine and sympathetic nervous activity to balance cardiometabolic homeostasis. Therefore, disrupted CNS leptin signaling is directly implicated in the development of metabolic diseases, such as hypertension, obesity, and type 2 diabetes. Independently, maternal leptin also plays a central role in the development and growth of the infant during gestation. Accumulating evidence points to the dynamic maternal leptin environment as a predictor of cardiometabolic fate in their offspring as it is directly associated with infant metabolic parameters at birth. In postnatal life, the degree of serum leptin is representative of the level of body adiposity/weight, a driving factor for cardiometabolic alterations, and therefore, the levels of blood leptin through the CNS mechanism, in a large part, are a strong determinant for future cardiometabolic fate. The current review focuses on highlighting and discussing recent updates for temporal dissection of leptin-associated programing of future cardiometabolic fate throughout the entire life.
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The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease.
Kiernan, K, MacIver, NJ
Frontiers in immunology. 2020;:622468
Abstract
Leptin is a critical mediator of the immune response to changes in overall nutrition. Leptin is produced by adipocytes in proportion to adipose tissue mass and is therefore increased in obesity. Despite having a well-described role in regulating systemic metabolism and appetite, leptin displays pleiotropic actions, and it is now clear that leptin has a key role in influencing immune cell function. Indeed, many immune cells have been shown to respond to leptin directly via the leptin receptor, resulting in a largely pro-inflammatory phenotype. Understanding the role of adipose-tissue derived mediators in inflammation is critical to determining the pathophysiology of multiple obesity-associated diseases, such as type 2 diabetes, autoimmune disease, and infection. This review, therefore, focuses on the latest data regarding the role of leptin in modulating inflammation.
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Interaction between genes involved in energy intake regulation and diet in obesity.
Crovesy, L, Rosado, EL
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:110547
Abstract
Obesity is a multifactorial, complex, and public health problem worldwide. Interaction between genes and environment as associated with diet may predispose an individual to obesity. In this sense, nutrigenetics appears to be a strategy that can improve understanding of the gene-diet interaction. The aim of this literature review was to summarize data from studies of genes involved in the regulation of energy intake (melanocortin 4 receptor [MC4R], fat mass and obesity-associated [FTO], ghrelin [GHRL], leptin [LEP], and cholecystokinin [CCK]) and diet interaction in obesity. The presence of polymorphisms in MC4R, FTO, leptin, and the respective receptor appear to be associated with higher energy and total lipid consumption. Polymorphisms in FTO, leptin, and leptin receptor are also related to increased intake of saturated fatty acids. Individuals with the MC4R, FTO, and ghrelin polymorphisms, who submitted themselves for weight loss intervention, appeared to achieve weight loss similar to individuals without polymorphisms in these genes. Additionally, protein seems to interact with these genes, which increases or decreases appetite, or to drive or lessen body weight recovery. Additionally, polymorphisms in these genes were found to be associated with inappropriate eating behaviors, such as increased consumption of sweets and snacks, consumption of large food portions, desire to eat, and eating associated with emotional issues. Preliminary data has supported the gene-diet interaction in determining weight loss and gain in individuals with polymorphisms in the genes involved in energy intake. Despite the advent of nutrigenetics in obesity, it is still too early to define the dietary management for weight loss based on the presence or absence of obesity polymorphisms.
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Relevance of Leptin and Other Adipokines in Obesity-Associated Cardiovascular Risk.
Landecho, MF, Tuero, C, Valentí, V, Bilbao, I, de la Higuera, M, Frühbeck, G
Nutrients. 2019;(11)
Abstract
Obesity, which is a worldwide epidemic, confers increased risk for multiple serious conditions including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue only for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins, and growth and vasoactive factors, which are collectively called adipokines known to influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. This review describes the relevance of specific adipokines in the obesity-associated cardiovascular disease.
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Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later?
Izquierdo, AG, Crujeiras, AB, Casanueva, FF, Carreira, MC
Nutrients. 2019;(11)
Abstract
Leptin, a hormone that is capable of effectively reducing food intake and body weight, was initially considered for use in the treatment of obesity. However, obese subjects have since been found to have high levels of circulating leptin and to be insensitive to the exogenous administration of leptin. The inability of leptin to exert its anorexigenic effects in obese individuals, and therefore, the lack of clinical utility of leptin in obesity, is defined as leptin resistance. This phenomenon has not yet been adequately characterized. Elucidation of the molecular mechanisms underlying leptin resistance is of vital importance for the application of leptin as an effective treatment for obesity. Leptin must cross the blood-brain barrier (BBB) to reach the hypothalamus and exert its anorexigenic functions. The mechanisms involved in leptin transportation across the blood-brain barrier continue to be unclear, thereby preventing the clinical application of leptin in the treatment of obesity. In recent years, new strategies have been developed to recover the response to leptin in obesity. We have summarized these strategies in this review.
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Effect of Conjugated Linoleic Acid Supplementation on Serum Leptin Concentration: A Systematic Review and Meta-Analysis.
Haghighatdoost, F, Hariri, M
Endocrine, metabolic & immune disorders drug targets. 2018;(3):185-193
Abstract
BACKGROUND There are controversies regarding the effect of conjugated linoleic acid (CLA) on serum leptin. OBJECTIVE To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of CLA on serum leptin concentrations. METHOD Databases such as Ovid, PubMed/Medline, SCOPUS, Google Scholar, and ISI databases up to January 2017 were searched. The searches included RCTs conducted among human adults, and studies on the effect of conjugated linoleic acid on serum leptin concentrations as outcome variables. The mean difference and standard deviation of leptin changes in the intervention and control groups were used as effect size measures for the meta-analysis. RESULT Eleven trials with thirteen effect sizes were pooled in this meta-analysis. CLA supplementations could not reduce serum leptin levels significantly (-0.12 (ng/ml); 95% CI: -1.29, 1.05; P=0.837). However, the impact of CLA supplementation differed by sex and BMI status. Compared with the control group, CLA administration reduced serum leptin levels significantly in trials conducted among male (- 0.86 (ng/ml); 95% CI: -1.11, -0.62; P<0.0001) or overweight individuals (-1.37 (ng /ml); 95% CI: -2.55, -0.20; P=0.022) and lasted for less than 8 weeks (-0.90 (ng/ml); 95% CI: -1.64, -0.17; P=0.0.016). CONCLUSION CLA supplementation might be able to decrease circulating leptin levels in studies with duration of less than 8 weeks especially among male and overweight subjects. Additional RCTs that are well controlled for energy intakes may be necessary to explain the cause of short- and long-term effects of conjugated linoleic acid. The protocol was registered with PROSPERO (No. CRD42017059165).
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Leptin: A new therapeutic target for treatment of diabetes mellitus.
Rehman, K, Akash, MSH, Alina, Z
Journal of cellular biochemistry. 2018;(7):5016-5027
Abstract
Leptin is an endogenous protein having 167 amino acids and is derived from adipocytes. It has tertiary structure that resembles with that of the pro-inflammatory cytokines family. The fundamental role of leptin is to maintain the energy homeostasis with the aid of its counter hormone called ghrelin, known as the "hunger hormone." Small quantities of leptin are also present in various tissues like ovary, placenta, pituitary gland, mammary gland, skeletal muscle, stomach, and lymphoid tissue. Expression of leptin is strongly associated with various inflammatory responses and immune system, and plays crucial role in the pathophysiology of obesity and development of diabetes mellitus (DM) and insulin resistance. The metabolic action of leptin is equally important as that of insulin in the pathophysiology of obesity and DM. Thereby, this review article tends to discuss the diverse and complicated role of leptin in the pathogenesis of DM. Furthermore, this article will highlight the signifying role of leptin as a therapeutic target by indicating the targeted treatment of DM through the appropriate understanding of advanced therapeutic approaches using leptin as a treatment strategy for DM.