-
JCI Insight Sep 2023Obesity promotes triple-negative breast cancer (TNBC), and effective interventions are urgently needed to break the obesity-TNBC link. Epidemiologic studies indicate...
Obesity promotes triple-negative breast cancer (TNBC), and effective interventions are urgently needed to break the obesity-TNBC link. Epidemiologic studies indicate that bariatric surgery reduces TNBC risk, while evidence is limited or conflicted for weight loss via low-fat diet (LFD) or calorie restriction (CR). Using a murine model of obesity-driven TNBC, we compared the antitumor effects of vertical sleeve gastrectomy (VSG) with LFD, chronic CR, and intermittent CR. Each intervention generated weight and fat loss and suppressed tumor growth relative to obese mice (greatest suppression with CR). VSG and CR regimens exerted both similar and unique effects, as assessed using multiomics approaches, in reversing obesity-associated transcript, epigenetics, secretome, and microbiota changes and restoring antitumor immunity. Thus, in a murine model of TNBC, bariatric surgery and CR each reverse obesity-driven tumor growth via shared and distinct antitumor mechanisms, and CR is superior to VSG in reversing obesity's procancer effects.
Topics: Humans; Mice; Animals; Triple Negative Breast Neoplasms; Caloric Restriction; Disease Models, Animal; Obesity; Bariatric Surgery
PubMed: 37698918
DOI: 10.1172/jci.insight.172868 -
Peptides Jul 2024Recent advancements in understanding glucagon-like peptide 2 (GLP-2) biology and pharmacology have sparked interest in targeting the GLP-2 receptor (GLP-2R) in the... (Review)
Review
Recent advancements in understanding glucagon-like peptide 2 (GLP-2) biology and pharmacology have sparked interest in targeting the GLP-2 receptor (GLP-2R) in the treatment of obesity. GLP-2 is a proglucagon-derived 33-amino acid peptide co-secreted from enteroendocrine L cells along with glucagon-like peptide 1 (GLP-1) and has a range of actions via the GLP-2R, which is particularly expressed in the gastrointestinal tract, the liver, adipose tissue, and the central nervous system (CNS). In humans, GLP-2 evidently induces intestinotrophic effects (i.e., induction of intestinal mucosal proliferation and improved gut barrier function) and promotes mesenteric blood flow. However, GLP-2 does not seem to have appetite or food intake-reducing effects in humans, but its gut barrier-promoting effect may be of interest in the context of obesity. Obesity is associated with reduced gut barrier function, increasing the translocation of proinflammatory gut content to the circulation. This phenomenon constitutes a strong driver of obesity-associated systemic low-grade inflammation, which in turn plays a major role in the development of most obesity-associated complications. Thus, the intestinotrophic and gut barrier-improving effect of GLP-2, which in obese rodent models shows strong anti-inflammatory potential, may, in combination with food intake-reducing strategies, e.g., GLP-1 receptor (GLP-1) agonism, be able to rectify core pathophysiological mechanism of obesity. Here, we provide an overview of GLP-2 physiology in the context of obesity pathophysiology and review the pharmacological potential of GLP-2R activation in the management of obesity and related comorbidities.
Topics: Humans; Obesity; Glucagon-Like Peptide-2 Receptor; Glucagon-Like Peptide 2; Animals
PubMed: 38579917
DOI: 10.1016/j.peptides.2024.171210 -
Journal of Lipid Research Dec 2023Perilipin 2 (Plin2) binds to the surface of hepatic lipid droplets (LDs) with expression levels that correlate with triacylglyceride (TAG) content. We investigated if...
Perilipin 2 (Plin2) binds to the surface of hepatic lipid droplets (LDs) with expression levels that correlate with triacylglyceride (TAG) content. We investigated if Plin2 is important for hepatic LD storage in fasted or high-fat diet-induced obese Plin2 and Plin2 mice. Plin2 mice had comparable body weights, metabolic phenotype, glucose tolerance, and circulating TAG and total cholesterol levels compared with Plin2 mice, regardless of the dietary regime. Both fasted and high-fat fed Plin2 mice stored reduced levels of hepatic TAG compared with Plin2 mice. Fasted Plin2 mice stored fewer but larger hepatic LDs compared with Plin2 mice. Detailed hepatic lipid analysis showed substantial reductions in accumulated TAG species in fasted Plin2 mice compared with Plin2 mice, whereas cholesteryl esters and phosphatidylcholines were increased. RNA-Seq revealed minor differences in hepatic gene expression between fed Plin2 and Plin2 mice, in contrast to marked differences in gene expression between fasted Plin2 and Plin2 mice. Our findings demonstrate that Plin2 is required to regulate hepatic LD size and storage of neutral lipid species in the fasted state, while its role in obesity-induced steatosis is less clear.
Topics: Animals; Mice; Lipid Droplets; Lipid Metabolism; Lipids; Liver; Obesity; Perilipin-2
PubMed: 37844775
DOI: 10.1016/j.jlr.2023.100461 -
Seminars in Cancer Biology Oct 2023Obesity, defined by excessive body fat, is a highly complex condition affecting numerous physiological processes, such as metabolism, proliferation, and cellular... (Review)
Review
Obesity, defined by excessive body fat, is a highly complex condition affecting numerous physiological processes, such as metabolism, proliferation, and cellular homeostasis. These multifaceted effects impact cells and tissues throughout the host, including immune cells as well as cancer biology. Because of the multifaceted nature of obesity, common parameters used to define it (such as body mass index in humans) can be problematic, and more nuanced methods are needed to characterize the pleiotropic metabolic effects of obesity. Obesity is well-accepted as an overall negative prognostic factor for cancer incidence, progression, and outcome. This is in part due to the meta-inflammatory and immunosuppressive effects of obesity. Immunotherapy is increasingly used in cancer therapy, and there are many different types of immunotherapy approaches. The effects of obesity on immunotherapy have only recently been studied with the demonstration of an "obesity paradox", in which some immune therapies have been demonstrated to result in greater efficacy in obese subjects despite the direct adverse effects of obesity and excess body fat acting on the cancer itself. The multifactorial characteristics that influence the effects of obesity (age, sex, lean muscle mass, underlying metabolic conditions and drugs) further confound interpretation of clinical data and necessitate the use of more relevant preclinical models mirroring these variables in the human scenario. Such models will allow for more nuanced mechanistic assessment of how obesity can impact, both positively and negatively, cancer biology, host metabolism, immune regulation, and how these intersecting processes impact the delivery and outcome of cancer immunotherapy.
Topics: Humans; Obesity; Body Mass Index; Neoplasms; Immunotherapy
PubMed: 37499846
DOI: 10.1016/j.semcancer.2023.07.004 -
Nutrients Dec 2023Consuming a diet that meets energy demands and provides essential nutrients promotes a healthy immune system, while both under- and over-nutrition have been associated... (Review)
Review
Consuming a diet that meets energy demands and provides essential nutrients promotes a healthy immune system, while both under- and over-nutrition have been associated with immune dysfunction. Military personnel comprise a unique population who frequently endure multi-stressor environments, predisposing them to immune decrements. Additionally, 49% and 22% of active duty U.S. military personnel are classified as overweight and obese, respectively. A literature search on PubMed was conducted to identify studies, reports, review papers, and references within those sources relevant to the topic area. Military personnel experiencing either under- or over-nutrition can suffer from degraded health, readiness, and performance. Insufficient intake of nutrients during military operations increases infection risk and negatively impacts infection recovery. Energy, protein, iron, zinc, and vitamins C and D are nutritional areas of concern that may impact immune competence in a multi-stressor environment. Over-nutrition can promote accretion of excess body fat and obesity, which contributes to a chronic inflammatory state that coincides with immune impairments. Prioritizing efforts to optimize nutrient intake is one approach for reducing disease burden and improving readiness. This review discusses nutritional concerns concomitant to multi-stressor environments that impact immune function, and the relevance of obesity to infectious disease risk in the military population.
Topics: Humans; Military Personnel; Nutritional Status; Obesity; Communicable Diseases; Immunity
PubMed: 38068857
DOI: 10.3390/nu15234999 -
Biology of Sex Differences Sep 2023We have previously reported that maternal obesity reduces placental transport capacity for lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA), a preferred form for...
BACKGROUND
We have previously reported that maternal obesity reduces placental transport capacity for lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA), a preferred form for transfer of DHA (omega 3) to the fetal brain, but only in male fetuses. Phosphatidylethanolamine (PE) and phosphatidylcholine (PC), have either sn-1 ester, ether or vinyl ether (plasmalogen) linkages to primarily unsaturated and monounsaturated fatty acids and DHA or arachidonic acid (ARA, omega 6) in the sn-2 position. Whether ether and plasmalogen PC and PE metabolism in placenta impacts transfer to the fetus is unexplored. We hypothesized that ether and plasmalogen PC and PE containing DHA and ARA are reduced in maternal-fetal unit in pregnancies complicated by obesity and these differences are dependent on fetal sex.
METHODS
In maternal, umbilical cord plasma and placentas from obese women (11 female/5 male infants) and normal weight women (9 female/7 male infants), all PC and PE species containing DHA and ARA were analyzed by LC-MS/MS. Placental protein expression of enzymes involved in phospholipid synthesis, were determined by immunoblotting. All variables were compared between control vs obese groups and separated by fetal sex, in each sample using the Benjamini-Hochberg false discovery rate adjustment to account for multiple testing.
RESULTS
Levels of ester PC containing DHA and ARA were profoundly reduced by 60-92% in male placentas of obese mothers, while levels of ether and plasmalogen PE containing DHA and ARA were decreased by 51-84% in female placentas. PLA2G4C abundance was lower in male placentas and LPCAT4 abundance was lower solely in females in obesity. In umbilical cord, levels of ester, ether and plasmalogen PC and PE with DHA were reduced by 43-61% in male, but not female, fetuses of obese mothers.
CONCLUSIONS
We found a fetal sex effect in placental PE and PC ester, ether and plasmalogen PE and PC containing DHA in response to maternal obesity which appears to reflect an ability of female placentas to adapt to maintain optimal fetal DHA transfer in maternal obesity.
Topics: Infant; Female; Humans; Male; Pregnancy; Placenta; Phosphatidylcholines; Phosphatidylethanolamines; Plasmalogens; Ether; Obesity, Maternal; Sex Characteristics; Chromatography, Liquid; Tandem Mass Spectrometry; Obesity; Ethyl Ethers; Ethers
PubMed: 37770949
DOI: 10.1186/s13293-023-00548-1 -
Philosophical Transactions of the Royal... Oct 2023The issue under discussion here is whether a decrease in the degree of UCP1 activity (and brown adipose tissue activity in general) could be a cause of obesity in... (Review)
Review
The issue under discussion here is whether a decrease in the degree of UCP1 activity (and brown adipose tissue activity in general) could be a cause of obesity in humans. This possibility principally requires the existence of the phenomenon of diet-induced thermogenesis. Obesity could be a consequence of a reduced functionality of diet-induced thermogenesis. Experiments in mice indicate that diet-induced thermogenesis exists and is dependent on the presence of UCP1 and thus of brown adipose tissue activity. Accordingly, many (but not all) experiments indicate that in the absence of UCP1, mice become obese. Whether similar mechanisms exist in humans is still unknown. A series of studies have indicated a correlation between obesity and low brown adipose tissue activity, but it may be so that the obesity itself may influence the estimates of brown adipose tissue activity (generally glucose uptake), partly explaining the relationship. Estimates of brown adipose tissue catabolizing activity would seem to indicate that it may possess a capacity sufficient to help maintain body weight, and obesity would thus be aggravated in its absence. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.
Topics: Humans; Obesity; Body Weight; Thermogenesis; Adipose Tissue, Brown; Diet
PubMed: 37661736
DOI: 10.1098/rstb.2022.0220 -
Archives of Gynecology and Obstetrics Mar 2024Obesity is recognized by the World Health Organization (WHO) as a disease in its own right. Moreover, obesity is an increasingly concerning public health issue across... (Review)
Review
Obesity is recognized by the World Health Organization (WHO) as a disease in its own right. Moreover, obesity is an increasingly concerning public health issue across the world and its prevalence is rising amongst women of reproductive age. The fertility of over-weight and obese women is reduced and they experience a higher rate of miscarriage. In pregnant women obesity not only increases the risk of antenatal complications, such as preeclampsia and gestational diabetes, but also fetal abnormalities, and consequently the overall feto-maternal mortality. Ultrasound is one of the most valuable methods to predict and evaluate pregnancy complications. However, in overweight and obese pregnant women, the ultrasound examination is met with several challenges, mainly due to an impaired acoustic window. Overall obesity in pregnancy poses special challenges and constraints to the antenatal care and increases the rate of pregnancy complications, as well as complications later in life for the mother and child.
Topics: Child; Female; Pregnancy; Humans; Obesity; Overweight; Diabetes, Gestational; Pregnancy Complications; Prenatal Care
PubMed: 37861742
DOI: 10.1007/s00404-023-07251-x -
PloS One 2023The World Health Organization (WHO) reported that the prevalence of obesity in the Kingdom of Saudi Arabia (KSA) is 33.7% (women 39.5% and men 29.5%), respectively. The...
BACKGROUND
The World Health Organization (WHO) reported that the prevalence of obesity in the Kingdom of Saudi Arabia (KSA) is 33.7% (women 39.5% and men 29.5%), respectively. The effects of obesity on airway inflammation and respiratory mechanics as well as the function of adipose tissue has a key role in the development of various lung diseases. Therefore, this study aimed to compare the level of cytokines between obese (BMI ≥ 30) and non-obese participants and to assess their association with BMI, airways inflammation and pulmonary function.
METHOD
One-hundred and seven non-smoking students (18-25 years of age) were recruited using convenience sampling technique for comparative cross-sectional study. Of them, 80 students were eligible and included in the analysis; 54 were non-obese (BMI<30) and 26 were obese (BMI ≥ 30). All the participants underwent anthropometric measurements, fractional exhaled nitric oxide (FeNO) measurement, spirometry and cytokines measurement (IL-6, IL-1β, GM-CSF, IL-7, IL-8 and IL-10). Measurements were compared between obese and non-obese groups. Then a correlation test was made between pro- and anti-inflammatory cytokines with BMI, pulmonary function test finding and FeNO.
RESULTS
The prevalence of obesity was 32.5% in the study population. Levels of pro-inflammatory cytokine IL-6 levels was significantly higher in obese than non-obese participants (p = 0.044). The level of FeNO log was significantly higher in obese participants than non-obese (p = 0.002). The pro-inflammatory cytokine IL-6 showed positive correlation with BMI while GMCSF showed negative correlation with FVC (p<0.05).
CONCLUSION
The levels of pro-inflammatory cytokine IL-6 was found to be significantly higher in obese participants than non-obese participants. Furthermore, it showed positive correlation with BMI whereas pro-inflammatory cytokine GMCSF showed negative correlation with FVC.
Topics: Male; Humans; Female; Cytokines; Cross-Sectional Studies; Interleukin-6; Obesity; Inflammation; Respiratory Function Tests; Body Mass Index
PubMed: 37992066
DOI: 10.1371/journal.pone.0294592 -
Primary Health Care Research &... Jan 2024This qualitative systematic review aimed to synthesise existing qualitative research on HCPs' perceptions and experiences of obesity and its management in primary care... (Review)
Review
AIM
This qualitative systematic review aimed to synthesise existing qualitative research on HCPs' perceptions and experiences of obesity and its management in primary care settings.
BACKGROUND
Healthcare professionals (HCPs), particularly those in primary care, play a key role in policy implementation around weight management. Overweight and obese individuals are subject to weight stigma which has negative health consequences and reduces the likelihood of healthcare service usage. An understanding of HCPs' perceptions of obesity and weight management in primary care is necessary for the development and delivery of effective initiatives.
METHODS
A search strategy developed using the SPIDER framework was applied to Medline and CINAHL databases. Inclusion criteria were applied, and quality assessment was undertaken using the CASP framework. Fifteen papers meeting the inclusion criteria were analysed thematically.
FINDINGS
Four themes were identified: conflicting discourses surrounding obesity, medicalisation of obesity, organisational factors, and lack of patient knowledge and motivation. Conflicting discourses around obesity refers to the differing views of HCPs regarding what it means to have and treat obesity. Medicalisation of obesity considers whether obesity should be treated as a medical condition. Organisational factors were identified as knowledge, resources and time that affected HCPs' ability to provide care to overweight or obese. Finally, the review discovered that patients required their own knowledge and motivation to lose weight. This review has highlighted the need to provide safe, non-judgemental spaces for HCPs and patients to discuss weight and weight loss. This is essential to the therapeutic relationship and the provision of effective obesity management.
Topics: Humans; Overweight; Obesity; Weight Loss; Health Personnel; Qualitative Research; Delivery of Health Care; Primary Health Care
PubMed: 38229563
DOI: 10.1017/S1463423623000683