Obesity
From the Editors:
From Fundamentals to the Clinic: Advancing Obesity Research in Endocrinology
Zeynep Madak-Erdogan, Stephen R Hammes, M Furkan Burak
Journal of the Endocrine Society is proud to publish a range of cutting-edge obesity research, furthering our scientific understanding in the field. The Editors encourage readers engaged in their own obesity or obesogen research to submit contributions on the topic and join our global community of authors.
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Explore the many benefits of publishing your work in our respected, fully open access journal, and learn how to prepare your manuscript for submission.
We invite you to explore below curated collections of recent, high-quality obesity papers published in the journal, selected by Editor-in-Chief Zeynep Madak-Erdogan, PhD. Articles included in this special collection span several critical topics in the field:
Genetic Associations
Atypical progeroid syndrome (APS) comprises heterogeneous disorders characterized by variable degrees of fat loss, metabolic alterations, and comorbidities that affect skeleton, muscles, and/or the heart. We describe 3 patients that were referred to our center for the suspicion of lipodystrophy. ...
Background Preferential accumulation of fat in the upper body (apple shape) is associated with higher risk of developing metabolic syndrome relative to lower body fat (pear shape). We previously discovered that chromatin openness partially defined the transcriptome of preadipocytes isolated from ...
Context Rare homozygous or biallelic variants in POMC , PCSK1 , and LEPR can disrupt signaling through the melanocortin-4 receptor (MC4R) pathway, resulting in hyperphagia and severe early-onset obesity. In pivotal Phase 3 clinical trials, treatment with the MC4R agonist setmelanotide reduced ...
Context Metabolic disorders such as obesity represent a major health challenge. Obesity alone has reached epidemic proportions, with at least 2.8 million people worldwide dying annually from diseases caused by overweight or obesity. The brain–metabolic axis is central to maintain homeostasis under ...
Hormones Related to Obesity
Context Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are increased in type 2 diabetes and are potential regulators of metabolism. The effect of changes in caloric intake and macronutrient composition on their circulating levels in patients with type 2 diabetes ...
Context Glucagon is produced and released from the pancreatic alpha-cell to regulate glucose levels during periods of fasting. The main target for glucagon action is the liver, where it activates gluconeogenesis and glycogen breakdown; however, glucagon is postulated to have other roles within the ...
Context Hyperglucagonemia may develop in type 2 diabetes due to obesity-prone hepatic steatosis (glucagon resistance). Markers of glucagon resistance (including the glucagon-alanine index) improve following diet-induced weight loss, but the partial contribution of lowering hepatic steatosis vs body ...
Context Adiponectin is an adipokine mainly secreted by adipocytes that regulates the metabolism of lipids and glucose. Liver receptor homolog-1 (LRH-1), also named NR5A2, is a nuclear receptor that regulates lipid metabolism and homeostasis. Objective The purpose of this study was to compare ...
Background The novel liver-gut hormone liver-expressed antimicrobial peptide-2 (LEAP2) is a centrally acting inverse agonist, and competitive antagonist of orexigenic acyl ghrelin (AG), at the GH secretagogue receptor, reducing food intake in rodents. In humans, the effects of LEAP2 on eating ...
Obesity-Related Conditions
Context Bariatric surgery has been shown to be effective in inducing complete remission of type 2 diabetes in adults with obesity. However, its efficacy in achieving complete diabetes remission remains variable and difficult to predict before surgery. Objective We aimed to characterize bariatric ...
Acute estrogen deficiency in women can occur due to many conditions including hyperprolactinemia, chemotherapy, GnRH agonist treatment, and removal of hormone replacement therapy. Ovariectomized (OVX) rodent models, often combined with a high-fat diet (HFD), have been used to investigate the ...
Context Metabolic flexibility is the physiologic acclimatization to differing energy availability and requirement states. Effectively maintaining metabolic flexibility remains challenging, particularly since metabolic dysregulations in meal consumption during cardiometabolic disease (CMD) ...
Context From previous studies, decreased thermogenesis and metabolic rate in the patients with overt and subclinical hypothyroidism lead to an increase in visceral adipose tissue (VAT) incidence, and which was associated with cardiovascular diseases. In this paper, we want to explore the ...
Context Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women. Objective This work examines whether an elevated serum T/A4 ...
Context Multiple studies suggest that adults who were normal weight at diabetes diagnosis are at higher risk for all-cause mortality than those who had overweight or obesity at diagnosis. Objective While obesity is a known risk factor for cardiometabolic disease, differences in body fat ...
Context The association between primary aldosteronism and obesity, especially its sex difference, remains unknown. Objective To assess the association for each subtype of primary aldosteronism with obesity parameters including visceral adipose tissue and differences between sexes. Methods In this ...
Context Children with X-linked hypophosphatemic (XLH) rickets have muscle weakness that severely impairs their function. Intermuscular and intramuscular adipose tissue (IMAT and intraMAT, respectively) may contribute to this muscle weakness. Objective This work aimed to compare IMAT and intraMAT in ...
Context The relationship of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with bone mineral density (BMD) is not well established. Objective To examine the associations of VAT and SAT with total body BMD in a large, nationally representative population with a wide range of ...
Context Metabolic syndrome (MetS) is associated with increased risk of severe COVID-19. MetS inflammatory biomarkers share similarities with those of COVID-19, yet this association is poorly explored. Objective Biomarkers of COVID-19 patients with and without MetS, the combination of diabetes, ...
Context Ovarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1 11β-hydroxysteroid dehydrogenase, which modulate peripheral androgen and cortisol production. Objectives To compare serum ...
In mammals, adipose tissues and skeletal muscles (SkMs) play a major role in the regulation of energy homeostasis. Recent studies point to a possibility of dynamic interplay between these 2 sites during development that has pathophysiological implications. Among adipose depots, brown adipose tissue ...
Ovarian reserve and fertility are reduced by aging and a poor energy balance. To date, the relationships of high energy accumulation and aging with the ovarian reserve have not been elucidated. Here, the effects of obesity on the aging ovarian reserve were evaluated in a leptin-deficient ( ob / ob ...
Obstructive sleep apnea (OSA), independently of obesity (OBS), predisposes to insulin resistance (IR) for largely unknown reasons. Because OSA-related intermittent hypoxia triggers lipolysis, overnight increases in circulating free fatty acids (FFAs) including palmitic acid (PA) may lead to ectopic ...
Context Ovarian estradiol supports female sexual behavior and metabolic function. While ovariectomy (OVX) in rodents abolishes sexual behavior and enables obesity, OVX in nonhuman primates decreases, but does not abolish, sexual behavior, and inconsistently alters weight gain. Objective We ...
Objective We aimed to explore the effect of weight change on abdominal aortic calcification (AAC) among men. Methods Data were obtained from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES). Self-reported cardiovascular disease patients were excluded. Lateral spine images ...
Context Turner syndrome (TS) is a rare genetic syndrome with an increased mortality, mainly attributed to cardiovascular disease. Objective This work aimed to investigate and correlate the lipid profile in adult women with TS to clinical characteristics. Methods A 12-year prospective cohort study, ...
Obesity Disparities
Context High childhood obesity rates coincide with increased incidence of nonalcoholic fatty liver disease (NAFLD) and other comorbidities. Understanding the genetics of susceptibility to obesity and its comorbidities could guide intervention. The cyclic adenosine monophosphate (cAMP)–dependent ...
Increased circulating fibroblast growth factor (FGF)-21 and sclerostin levels have been reported in patients with type 2 diabetes (T2D). We assessed the association of FGF-21 and sclerostin with adiposity, glycemia, and glucoregulatory measures in healthy subjects. We studied 20 normoglycemic Black ...
Objectives Obesity is a risk factor for type 2 diabetes (T2D), but prospective data relating adiposity measures to incident prediabetes are scant. Methods The Pathobiology of Prediabetes in A Biracial Cohort study followed normoglycemic African Americans (AA) and European Americans (EA) with ...
Context Polycystic ovary syndrome (PCOS) is common and associated with metabolic syndrome. In the general population, metabolic disease varies by race and ethnicity. Objective This work aimed to examine in depth the interaction of race and ethnicity with PCOS-related metabolic disease in adolescent ...
Pediatrics and Obstetrics
Context In utero exposure to maternal obesity or diabetes is considered a pro-inflammatory state. Objective To evaluate whether cord blood proprotein convertase subtilisin/kexin-type 9 (PCSK9), which is regulated by inflammation and metabolic derangements, is elevated in neonates born to ...
Context Controversy exists regarding associations between early-life growth patterns and timing of puberty. Objective This work aims to investigate associations between birth anthropometry, early growth patterns, and onset/progression of pubertal milestones in boys and girls. Methods Among children ...
Context Prepubertal obesity is a well-established predictor of earlier pubertal onset, which is itself a risk factor for poor health and well-being. Identifying specific patterns of weight gain in early life may help explain differential risk for earlier pubertal onset. Objective The objective of ...
Context Small-for-gestational-age (SGA) children have a particular metabolic and hormonal pattern at birth that changes rapidly. Objective To evaluate the linear and weight growth in the first year of life in SGA children. Design Prospective, monocentric cohort study. Setting Real-world data ...
Context Adults with cerebral palsy (CP) display a higher prevalence of cardiometabolic disease compared with the general population. Studies examining cardiometabolic disease risk in children with CP are limited. Objective The purpose of this study was to determine if children with CP exhibit ...
Context Obesity surveillance is scarce in adolescents, and little is known on whether salivary metabolomics data, emerging minimally invasive biomarkers, can characterize metabolic patterns associated with overweight or obesity in adolescents. Objective This pilot study aims to identify the ...
Context Insulin resistance, glucose alterations, arterial hypertension (HTN), and the renin–angiotensin–aldosterone system (RAAS) are related in adult obesity. This crosstalk is still unexplored in childhood. Objective Characterize the relationships of fasting and postload glucose and insulin ...
With the declining age at onset of puberty and increasing prevalence of childhood obesity, early breast development in young obese girls has become a more frequent occurrence. Here, we examine available literature to answer a series of questions regarding how obesity impacts the evaluation and ...
One in seven couples in developed countries suffers from infertility. Maternal overweight or obesity have detrimental and lasting effects on offspring cardiometabolic health, and although substantially more data are needed, hormonal imbalances in utero resulting from excessive maternal adiposity ...
Context The shift in maternal energy metabolism characteristic of pregnancy is thought to be driven by various hormonal changes, especially of ovarian and placental steroids. Imbalances in circulating estradiol (E 2 ) and progesterone (P 4 ) levels during this period are often associated with ...
Possible Therapies
Context Bariatric surgery has been shown to be effective in inducing complete remission of type 2 diabetes in adults with obesity. However, its efficacy in achieving complete diabetes remission remains variable and difficult to predict before surgery. Objective We aimed to characterize bariatric ...
Context Despite a high prevalence of obesity in the veteran population, antiobesity medications (AOMs) have been underused in the Veterans Health Administration. Real-world reports on outcomes when AOMs have been used in veterans is limited. Objective To analyze weight loss outcomes from a local ...
Context Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are increased in type 2 diabetes and are potential regulators of metabolism. The effect of changes in caloric intake and macronutrient composition on their circulating levels in patients with type 2 diabetes ...
Context According to the carbohydrate-insulin model of obesity, an elevated insulin-to-glucagon ratio in response to a high-carbohydrate diet directs metabolic fuels toward storage, resulting in lower circulating energy. Objective To determine differences in total circulating energy post-meal ...
Context Research in lipodystrophy (LD) and its treatment with metreleptin has not only helped patients with LD but has opened new directions in investigating leptin's role in metabolism and the regulation of eating behavior. Previously, in a study with patients with LD undergoing metreleptin ...
Context Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy. Objective To determine whether 8 weeks of intranasal OXT (vs 8 weeks of placebo) promotes weight loss in ...
Context The Pritikin Program, which provides intensive lifestyle therapy, has been shown to improve cardiometabolic outcomes when provided as a residential program. Objective The purpose of the present study was to conduct a short-term, randomized, controlled trial to evaluate the feasibility and ...
Despite professional society guidelines recommending that obesity be treated as a chronic disease by emphasizing the use of lifestyle modification in conjunction with pharmacotherapy, antiobesity medications are uncommonly prescribed in most clinical practices. The recent Food and Drug ...
Obesity is associated with increased mortality as a result of several comorbidities which occur in tandem with the obese state. Chronic inflammation is well documented in obesity, and evidence from numerous studies support the notion that the increased inflammation in individuals with obesity ...
Testosterone (T) administration (TA) increases serum T and fat-free mass (FFM). Although TA-mediated increases in FFM may enhance physical performance, the data are largely equivocal, which may be due to differences in study populations, the magnitude of change in serum T and FFM, or the ...
Context and objective Obesity and inactivity are risk factors for developing impaired glucose tolerance characterized by insulin resistance and reduced beta-cell function. The stimulatory effect of glucagon-like peptide 1 (GLP-1) on insulin secretion is also impaired in obese, inactive individuals. ...
The discovery of bioactive peptides is an important research target that enables the elucidation of the pathophysiology of human diseases and provides seeds for drug discovery. Using a large number of native peptides previously identified using plasma peptidomics technology, we sequentially ...
To explore the mechanism by which intermittent fasting (IF) exerts prolonged effects after discontinuation, we examined mice that had been subjected to 4 cycles of fasting for 72 hours and ad libitum feeding for 96 hours per week (72hIF), followed by 4 weeks of ad libitum feeding, focusing on ...
Context Chronic high-fat diet (HFD) consumption causes obesity associated with retention of bile acids (BAs) that suppress important regulatory axes, such as the hypothalamic–pituitary–adrenal axis (HPAA). HFD impairs nutrient sensing and energy balance due to a dampening of the HPAA and reduced ...
Context The glucagon-like peptide-1 receptor (GLP-1R) agonist semaglutide (SEMA) produces 15% weight loss when chronically administered to humans with obesity. Methods In 2 separate experiments, rats received daily injections of either vehicle (VEH) or SEMA starting at 7 µg/kg body weight (BW) and ...
Background Different treatment modalities are available for obesity management, including lifestyle changes, pharmacotherapy, endoscopic interventions, and surgeries. Limited evidence is available on the weight loss effect of combining glucagon-like peptide 1 receptor agonists (GLP-1 RAs) with ...
