Search Results (231)

Obesity and metabolic dysfunction are established risk factors for luminal breast cancer, yet current preclinical models inadequately recapitulate the complex metabolic and immune interactions driving tumorigenesis. To develop and characterize an immunocompetent rat model of luminal breast cancer induced by chronic exposure to a cafeteria diet mimicking Western obesogenic nutrition, female rats were fed a cafeteria diet or standard chow from weaning. Metabolic parameters, plasma biomarkers (including leptin, insulin, IGF-1, adiponectin, and estrone), mammary gland histology, tumor incidence, and gene expression profiles were longitudinally evaluated. Gene expression was assessed by PCR arrays and qPCR. A subgroup underwent dietary reversal to assess the reversibility of molecular alterations. Cafeteria diet induced significant obesity (mean weight 426.76 g vs. 263.09 g controls, p < 0.001) and increased leptin levels without altering insulin, IGF-1, or inflammatory markers. Histological analysis showed increased ductal ectasia and benign lesions, with earlier fibroadenoma and luminal carcinoma development in diet-fed rats. Tumors exhibited luminal phenotype, low Ki67, and elevated PAI-1 expression. Gene expression alterations were time point specific and revealed early downregulation of ID1 and COX2, followed by upregulation of MMP2, THBS1, TWIST1, and PAI-1. Short-term dietary reversal normalized several gene expression changes. Overall tumor incidence was modest (~12%), reflecting early tumor-promoting microenvironmental changes rather than aggressive carcinogenesis. This immunocompetent cafeteria diet rat model recapitulates key metabolic, histological, and molecular features of obesity-associated luminal breast cancer and offers a valuable platform for studying early tumorigenic mechanisms and prevention strategies without carcinogen-induced confounders. Full article

The most frequently used laboratory animals for studies on adipose tissue properties and obesity are rodents. However, there are significant differences in the types of visceral fat depots between rodents and humans, including fat depots in the heart area. The large human fat depot of greatest interest in cardiac research is the epicardial adipose tissue (EAT). Its properties are widely investigated, because the EAT lies directly on the heart’s surface and can easily affect myocardial physiology. The major fat depot in rodents‘ chest—pericardial fat—is located on the ventral surface of the parietal lamina of the pericardium and is often incorrectly referred to as the EAT. Further confusion arises from reports claiming that rodents are entirely devoid of the EAT. We decided to verify adipose tissues in the heart area of 16 male Sprague Dawley rats under physiological conditions and in obesity. The animals in the NFD group (n = 8) were fed with a standard diet while these in the HFD group (n = 8) were fed with a high-fat diet (31% fat) starting from 4 weeks after birth. When the animals reached 12 weeks, the presence of fat deposits was verified. Additionally, their blood was collected to characterize carbohydrate and lipid metabolism changes, adipokine profile alterations, and their systemic inflammation status. The obesogenic diet caused significant disturbances in their carbohydrate and lipid metabolism, as well as hyperleptinemia. A high-fat diet primarily promoted the accumulation of pericardial fat, which was absent in the NFD rats and observed in 6 out of the 8 HFD animals. In both groups, adipocytes were also found directly on the hearts’ surfaces (EAT), albeit in very small numbers and limited to the atrioventricular groove on the dorsal side of the hearts. These adipocytes were dispersed among the vessels, making quantitative assessment and separation difficult, however, macroscopic evaluation revealed no noticeable differences in its extent. In conclusion, although rats are not entirely devoid of the EAT, their suitability for studying the properties of the EAT appears to be considerably limited. Full article

Background: Worldwide, the awareness about childhood obesity as a public health concern is increasing, particularly in developing countries like Pakistan. Obesity during early childhood may persist into later ages, increasing the risk of chronic illnesses such as diabetes and hypertension. Objective: The aim of this study was to examine the relationship of different types of food groups with obesity among children with normal and stunted growth trajectories in Pakistan. Methods: This cross-sectional study conducted a secondary analysis of Pakistan Demographic and Health Surveys (PDHSs) conducted in the years 2012–2013 and 2017–2018. Data of 1230 healthy and obese children with either normal or stunted growth were analysed after excluding those who were aged below six months, wasted, underweight, or had missing anthropometric or dietary data. The relationship of different food groups with obesity among the children with normal and stunted growth was analysed by bivariate logistic regression. Results: The prevalence of paediatric obesity dropped from 7.3% in 2012–2013 to 2.4% in 2017–2018. However, the coexistence of stunting with obesity—termed the nutritional paradox—slightly increased from 2.8% in 2012–2013 to 3% in 2017–2018. Among the different food groups, the continuation of breastmilk was associated with lowering the odds of obesity by 69% (25% to 88%) among children with normal growth. Conversely, among children with stunted growth, the continuation of breastmilk was associated with an increase in the odds of obesity by 3.71 (1.08 to 12.62) times. Conclusion: Despite the 4.9% reduction in paediatric obesity, cases of the nutritional paradox are still escalating in Pakistan. This reflects an urgent need for targeted nutritional interventions to mitigate the impact of obesogenic diets and reduce the prevalence of childhood obesity in Pakistan. Full article

The association between aluminum exposure and obesity remains uncertain. This study investigated whether aluminum exposure (dietary, serum, and urinary) is linked to obesity and whether dietary antioxidant capacity moderates this relationship. A total of 54 adult women (26 obese, 28 normal weight) were recruited from a private weight loss clinic in Türkiye. Dietary aluminum exposure was estimated using 24 h dietary recalls and literature values, and antioxidant capacity was calculated through a food frequency questionnaire. Serum and spot urine samples were collected, and aluminum levels were measured using inductively coupled plasma optical emission spectrometry. No significant differences were observed between normal weight and obese groups in serum aluminum (127.7 ± 102.42 vs. 122.9 ± 88.37 µg/L, p > 0.05), urinary aluminum (28.1 ± 12.73 vs. 14.1 ± 10.77 µg/L, p > 0.05), or weekly dietary aluminum exposure (0.61 ± 0.45 vs. 0.45 ± 0.24 mg/kg bw/week, p > 0.05). Dietary aluminum exposure correlated positively with total antioxidant capacity (r = 0.665, p < 0.001). Regression analysis revealed that dietary aluminum exposure was inversely associated with body mass index (β = −0.27, p < 0.05), while antioxidant capacity did not moderate this relationship, nor did the age difference. These results suggest dietary aluminum exposure reflects diet quality and/or food preparation methods, etc., rather than directly influencing obesity. Full article

Next to adrenergic signalling, purinergic pathways mediated by extracellular adenine nucleotides have been described to shape thermogenic and metabolic functions in brown adipose tissue (BAT). Here we describe high expression of P2X5 that is activated by ATP in mature adipocytes of BAT and differentiated brown adipocytes in vitro. The levels of other P2X family members were much lower, or expression was restricted to tissue-resident macrophages or endothelial cells. Global and brown adipocyte-specific P2rx5 deficiency resulted in lower expression of the uncoupling protein 1 (UCP1). However, indirect calorimetry studies showed that P2X5 did not affect systemic energy expenditure. Of note, glucose tolerance was impaired under chow and obesogenic high-fat diet conditions, which can be explained by lower glucose disposal into BAT but not into other organs. In summary, these data indicate a modulatory role of P2X5 in systemic and BAT-specific glucose metabolism. Full article

Background/Objectives: Diets high in simple carbohydrates and saturated fats, commonly consumed in Westernized countries, have been linked to a greater predisposition to metabolic disorders, which are partly attributed to oxidative stress. This study aimed to investigate the impact of an obesogenic diet consumed during the pregnancy and lactation periods on hepatic metabolism and REDOX balance in rats. Methods: Sixteen pregnant Wistar rats were divided into two groups: control (CD), which received a vivarium diet, and obesogenic (OD), which received an obesogenic diet (high-fat diet plus condensed milk), from early pregnancy to late lactation. Thirty-six hours after weaning, the rats were euthanized, and blood, adipose tissue, and liver samples were collected for analysis. Results: These results demonstrate that exposure to an obesogenic diet during pregnancy and lactation in rats leads to adverse changes in hepatic metabolic, inflammatory, and REDOX balance. This experimental animal model serves as a valuable tool for investigating the mechanisms of metabolic dysfunction associated with diets that mimic human eating habits. However, it is essential to note that these findings pertain to an experimental model and therefore require validation in clinical studies to confirm their relevance and applicability in human health. Conclusions: The consumption of an obesogenic diet during pregnancy and lactation in rats induces adverse alterations in hepatic metabolic, inflammatory, and redox homeostasis. This animal model helps investigate the mechanisms of metabolic dysfunctions associated with human dietary habits. However, these findings still need to be confirmed in clinical studies to verify their relevance in humans. Full article

Heat-inactivated probiotics, also known as postbiotics, have emerged as an alternative to live probiotics, and have been shown to be good therapeutic tools for the management and treatment of metabolic dysfunctions such as obesity and type 2 diabetes (T2D). The present study aimed to assess the anti-obesogenic and anti-diabetic properties of heat-inactivated Pediococcus acidilactici pA1c^® (pA1c^®HI) in mice fed a high-fat diet (HFD). The animals were given an HFD or HFD enriched with either the probiotic alive pA1c^® or the postbiotic pA1c^®HI. Body weight (BW), serum biochemical markers, gene expression, and histological changes were determined following 15 weeks of supplementation. The postbiotic pA1c^®HI exerted a similar effect on glucose metabolism to that exerted by pA1c^® supplementation. Nevertheless, we observed that pA1c^®HI supplementation maintained BW, attenuated adipogenesis, and protected the mice from liver damage more efficiently than pA1c^®. Similarly, in adipose tissue, pA1c^®HI significantly downregulated markers of de novo lipogenesis (DNL) and fat storage. The observed results show that pA1c^®HI administration was even more effective in mitigating the HFD’s detrimental effects than pA1c^® supplementation, and therefore, the viability of this Pediococcus acidilactici CECT 9879 strain is not required for preserving its beneficial properties in the context of obesity and T2D. Full article

Background and Objectives: Obesity is linked to liver cancer through metabolic mechanisms and can promote tumor growth through metabolic impairment, decreased lipid metabolism, and interference of the energy balance in the liver. NAMPT is an enzyme expressed in the liver and is involved in the progression of tumors in obesogenic environments, while iNAMPT is known to be the rate-limiting enzyme in the synthesis of NAD, an essential coenzyme involved in ATP synthesis which promotes a pro-growth environment in the context of obesity. Because iNAMPT and cellular energetics, a hallmark of cancer, play an important role in liver cancer progression, it has become a target for cancer therapies focused on inhibiting its functions. The objective of this study was to determine the contribution of NAD biosynthesis in obesity-associated liver cancer progression. Methods: Cell culture studies were conducted with serum from male mice randomized to diet-induced obesity (OB) or control (CR) ± FK866 (iNAMPT inhibitor) in SNU, HepG2 human liver cancer cells, and Hepa 1-6 liver murine cells. Protein analysis of pAkt and pErk was performed via immunoblot. Cytotoxicity, reactive oxygen species (ROS), cell viability, and invasion were also measured in the cells. For the mouse model, the C57BL/6J male mice were randomized to the DIO or CR group. At 21 weeks of age, the mice were injected subcutaneously with Hepa 1-6 liver cancer cells. At 23 weeks, the mice received an I.P. injection of FK866 (30 mg/kg) for 2 weeks. The tumor and mouse weights were measured. Results: The cells exposed to OB sera showed increased proliferation, lactate dehydrogenase (LDH) secretion, ROS, and invasion. FK866 decreased proliferation, LDH secretion, ROS, and invasion for all liver cancer cells. The cells exposed to CR sera and OB + FK866 resulted in more LDH, suggesting increased apoptosis compared with OB sera. The OB sera increased phosphorylation of Akt, which was suppressed by FK866 compared with the OB group. In liver cancer cells, physiological and cellular signaling is affected differently when inhibiting NAD biosynthesis in an in vitro model of obesity and liver cancer. In vivo, the diet-induced obese (DIO) mice weighed significantly more than the mice fed a control diet. In addition, 70% of the DIO mice developed tumors, compared with 20% of the CR mice, and had tumors with greater volumes and weights. NAD inhibition blocked obesity-induced tumor growth. Conclusions: In this study, we demonstrate that inhibition of iNAMPT resulted in suppression of tumor growth in the context of obesity. Identifying pre-clinical strategies to reverse the impact of obesity on liver cancer progression is important due to the strong increased risk of liver cancer and its poor prognosis. Future translational research studies can be built from this pre-clinical foundational research. Full article

C-phycocyanin (CPC), a bioactive compound derived from Spirulina, has been described as a molecule with antioxidant and anti-inflammatory properties. It has also been demonstrated that sustainably obtained CPC effectively inhibited body mass gain, regulated serum leptin and resistin levels, and prevented the onset of a pro-inflammatory state in Swiss mice fed a hyperlipidic diet. These results highlighted the anti-obesogenic potential of CPC. Brown adipose tissue (BAT) has been identified as a promising target in the treatment of obesity, playing a role in energy expenditure. In this study, Swiss mice fed a high-fat diet were supplemented with 500 mg/kg body weight of CPC daily for 12 and 16 weeks. BAT was collected, and Western blot and ELISA were performed. A reduction in pro-inflammatory cytokines, as well as a decrease in leptin levels was observed in the tissue, which was also associated with a reduction in BAT relative weight to body mass. Furthermore, CPC administration was able to modulate uncoupling protein 1 (UCP1) levels, which is crucial in the thermogenesis process. Therefore, this study demonstrated that supplementation with CPC reduces inflammatory cytokines associated with detrimental effects in the BAT, emerging as a tool in combating obesity and improving BAT function. Full article

Background/Objectives: Metabolic dysregulation underlies a myriad of chronic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity, and bile acids emerge as an important mediator in their etiology. Weight control by improving diet quality is the standard of care in prevention and control of these metabolic diseases. Inclusion of pulses, such as common bean, is an affordable yet neglected approach to improving diet quality and metabolic outcomes. Thus, this study evaluated the possibility that common bean alters bile acid metabolism in a health-beneficial manner. Methods: Using biospecimens from several similarly designed studies, cecal content, feces, liver tissue, and plasma samples from C57BL/6 mice fed an obesogenic diet lacking (control) or containing cooked common bean were subjected to total bile acid analysis and untargeted metabolomics. RNA-seq, qPCR, and Western blot assays of liver tissue complemented the bile acid analyses. Microbial composition and predicted function in the cecal contents were evaluated using 16S rRNA gene amplicon and shotgun metagenomic sequencing. Results: Bean-fed mice had increased cecal bile acid content and excreted more bile acids per gram of feces. Consistent with these effects, increased synthesis of bile acids in the liver was observed. Microbial composition and capacity to metabolize bile acids were markedly altered by bean, with greater prominence of secondary bile acid metabolites in bean-fed mice, i.e., microbial metabolites of chenodeoxycholate/lithocholate increased while metabolites of hyocholate were reduced. Conclusions: In rendering mice resistant to obesogenic diet-induced MASLD and obesity, cooked bean consumption sequesters bile acids, increasing their hepatic synthesis and enhancing their diversity through microbial metabolism. Bean-induced changes in bile acid metabolism have potential to improve dyslipidemia. Full article

The pathogenesis of obesity is complex and incompletely understood, with an underlying interplay between our genetic architecture and obesogenic environment. The public understanding of the development of obesity is shrouded in myths with widespread societal misconceptions. Body Mass Index (BMI) is a highly heritable trait. However, despite reports from recent genome-wide association studies, only a small proportion of the overall heritability of BMI is known to be lurking within the human genome. Other non-genetic heritable traits may contribute to BMI. The gut microbiome is an excellent candidate, implicating complex interlinks with hypothalamic control of appetite and metabolism via entero-endocrine, autonomic, and neuro-humeral pathways. The neonatal gut microbiome derived from the mother via transgenerational transmission (vaginal delivery and breastfeeding) tends to have a permanence within the gut. Conversely, non-maternally derived gut microbiota manifest mutability that responds to changes in lifestyle and diet. We should all strive to optimize our lifestyles and ensure a diet that is replete with varied and unprocessed plant-based foods to establish and nurture a healthy gut microbiome. Women of reproductive age should optimize their gut microbiome, particularly pre-conception, ante- and postnatally to enable the establishment of a healthy neonatal gut microbiome in their offspring. Finally, we should redouble our efforts to educate the populace on the pathogenesis of obesity, and the role of heritable (but modifiable) factors such as the gut microbiome. Such renewed understanding and insights would help to promote the widespread adoption of healthy lifestyles and diets, and facilitate a transition from our current dispassionate and stigmatized societal approach towards people living with obesity towards one that is epitomized by understanding, support, and compassion. Full article

A body of evidence indicates an association between ultraprocessed foods (UPFs) and health outcomes. Most of it has been obtained through preclinical studies, although a number of observational studies substantiate how a high intake of these products increases the risk of neuropsychiatric disorders, and an increasing amount of dietary intervention studies confirm these findings. The aim of this narrative review is to describe some of the putative mechanisms involved in the deleterious effects of a high intake of UPFs on neuropsychiatric outcomes. A myriad of unhealthy actions may be associated with the consumption of UPFs, and some mechanisms are being discussed. They include UPFs’ high caloric density; their high sugar, sodium, and additives content and low amounts of fiber; and a high palatability that induces overconsumption, acting as obesogens. Moreover, thermal treatment of these foods generates oxidative products such as glycotoxins, lipotoxins, and acrolein, all of which affect the brain. The chemical products act, directly or indirectly, on the gut microbiome and affect the gut–brain axis, causing neuroinflammation, oxidative stress, and neurodegeneration. UPFs also exert various epigenetic effects that affect mental health and might explain the intergenerational inheritance of neuropsychiatric disorders. A diet containing a high proportion of these foods has a low nutritional density, including bioactive protective agents such as antioxidant and anti-inflammatory compounds that promote eubiosis. The evidence shows that UPFs intake affects neuropsychiatric outcomes such as neurodegeneration, cognitive decline, dementia, and mood disorders and reinforces the need to promote a healthy dietary pattern throughout all life stages, thus interfering with the current commercial determinants of health. Full article

Perivascular adipose tissue (PVAT) regulates vascular tone and is composed of adipocytes and several leukocyte subpopulations. Diet can modify PVAT function, as obesogenic diets cause morphological changes to adipocytes and skew the leukocyte phenotype, leading to PVAT dysregulation and impaired vasoregulation. Of note, platelets, the clot-forming cells, also modulate many facets of leukocyte activity, such as tissue infiltration and polarity. We aimed to determine whether platelets regulate the leukocyte populations residing within PVAT. Male C57Bl/6J mice were fed a Western diet (30% kcal sucrose, 40% kcal fat, 8.0% sodium) to develop obesogenic conditions for PVAT leukocyte remodeling. Diet was either administered acutely (2 weeks) or extended (8 weeks) to gauge the length of challenge necessary for remodeling. Additionally, platelet depletion allowed for the assessment of platelet relevance in PVAT leukocyte remodeling. Abdominal PVAT (aPVAT) and thoracic PVAT (tPVAT) were then isolated and leukocyte composition evaluated by flow cytometry. Compared to control, Western diet alone did not significantly impact PVAT leukocyte composition for either diet length. Platelet depletion, independent of diet, significantly disrupted PVAT leukocyte content with monocytes/macrophages most impacted. Furthermore, tPVAT appeared more sensitive to platelet depletion than aPVAT, providing novel evidence of platelet regulation of leukocyte composition within PVAT depots. Full article

Background: Obesity is a multifactorial disease with detrimental effects on health and quality of life; unregulated satiety plays a crucial role in food intake and obesity development. Naringenin (NAR) has shown beneficial effects on lipid and carbohydrate metabolism, although its impact on adiposity and satiety remains unclear. This study reports a Western diet (WD)-induced obesity model in rats, wherein 100 mg/kg of NAR was administered as an anti-obesity agent for 8 weeks; oxidative stress, lipid profile, and satiety biomarkers were then studied, as well as in silico interaction between NAR and cholecystokinin (CCK) and ghrelin receptors. Results: NAR supplementation resulted in a significant decrease in retroperitoneal adipose tissue and liver weight, as compared to the untreated WD group (p < 0.05), potentially associated with a decreased feed efficiency. NAR also inhibited the development of dyslipidemia, particularly by reducing serum triglycerides (p < 0.05). NAR supplementation increased CCK serum levels in the basal diet group, an effect that was abolished by the WD (p < 0.05); likewise, no changes were determined on ghrelin (p > 0.05). In silico data shows that NAR is capable of interacting with the CCK and ghrelin receptors, which suggests a potential for it to modulate hunger/satiety signaling by interacting with them. Conclusions: We conclude that NAR has anti-obesogenic effects and may regulate CCK serum levels, although further research is still needed. Full article

Background/Objectives: The consumption of diets with high fat, salt, and sugar content has been associated with increasing the risk of developing a range of pathologies, including cardiovascular disease, obesity, and diabetes. Furthermore, there is growing evidence to suggest a relationship between variation in the nutritional environment and pancreatic dysregulation, which may be a consequence of oxidative stress. This study aimed to examine the effects of a high-fat, high-carbohydrate (obesogenic) maternal diet during pregnancy and lactation on the metabolic health and pancreatic structure of rat offspring. Methods: Pregnant rats were divided into two groups: one fed a standard diet and the other an obesogenic diet. After weaning, male pups from both groups were fed the same diet until they were 30 days old, which is when they were euthanized. Results: Metabolic and murinometric changes: Increased body weight and pancreas size, elevated blood glucose and cholesterol levels, and reduced glucose tolerance (which is indicative of the beginning of insulin resistance). Oxidative stress: Higher levels of oxidative damage markers and decreased antioxidants in the pancreas, suggesting a state of oxidative stress in this organ. Changes in pancreatic structure: Increased size and number of pancreatic islets and decreased size and number of pancreatic acini. Conclusions: A maternal obesogenic diet induces metabolic alterations, increases oxidative stress, and causes changes in the structure of the pancreas in rat offspring, suggesting a higher risk of developing metabolic diseases such as type 2 diabetes in adulthood. Full article