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1.
Nutrients ; 16(7)2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38612965

RESUMEN

The lipid accumulation product (LAP) is a reliable marker of metabolic syndrome, which includes conditions like obesity. However, the correlation between the circulating selenium (CSe) concentration and the LAP is currently unclear. This study aimed to ascertain this correlation. Overall, 12,815 adults aged ≥20 years were enrolled in this study. After adjusting for all the confounding variables, CSe was positively correlated to the LAP (ß = 0.41; 95% confidence interval [CI]: 0.28, 0.54; p < 0.001). Compared with the lowest quartile of CSe, the highest quartile of CSe was positively related to the LAP (ß = 0.16; 95% CI: 0.12, 0.21; p < 0.001). Moreover, the correlation between CSe and the LAP revealed a positive non-linear trend. In the subgroup analysis, interaction effects were observed for age, sex, smoking, and stroke (p for interaction < 0.05). The effects were stronger for males (ß = 0.64, 95% CI: 0.47, 0.80; p < 0.001) and individuals who smoke at the time of the trial (ß = 0.64, 95% CI: 0.37, 0.91; p < 0.001). In conclusion, our results indicated that CSe was positively correlated with the LAP in a non-linear manner. Future research is warranted to explore their relationship and better understand the mechanisms underlying this association.


Asunto(s)
Producto de la Acumulación de Lípidos , Síndrome Metabólico , Selenio , Adulto , Masculino , Humanos , Estudios Transversales , Síndrome Metabólico/epidemiología , Obesidad
2.
Open Vet J ; 14(1): 428-437, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38633156

RESUMEN

Background: Obesity is one of the most prevalent and perilous health affairs. Male obesity-associated secondary hypogonadism (MOSH) is one of many of its complexities, which is mounting in parallel with the aggravation of obesity. Magnetic nanoparticles seem to be an advanced favorable trend in multiple biomedical fields. Aim: In this study, we explore the therapeutic effects of superparamagnetic iron oxide nanoparticles (SPIONs) coated with carboxymethyl cellulose (CMC) on an obese male rat model with MOSH syndrome, comparing their impacts with a well-known anti-obesity medication (Orlistat). Methods: 42 male albino rats split into 7 equal groups: 1-negative control: nonobese, untreated; 35 rats fed the high fat-high fructose (HFHF) diet for a period of 12 weeks. Obese rats splitted into 6 equal groups; 2-positive control: obese untreated; 3-obese given Orlistat (30 mg/kg); 4-obese given CMC-SPIONs (25 mgFe/kg); 5-obese given CMC-SPIONs (50 mgFe/kg); 6-obese given CMC-SPIONs(25 mgFe/kg) + Orlistat (30 mg/kg), 7-obese given CMC-SPIONs (50 mgFe/kg) + Orlistat (30 mg/kg); all treatments given orally for 4 weeks. During sacrifice, blood serum and sectioned hypothalamic, pituitary, testicular, and adipose tissues were collected for biochemical and biomolecular assessments. Results: The HFHF diet for 12 weeks resulted in a significant upsurge in body weight, body mass index, serum fasting glucose, insulin resistance, TAG, total cholesterol, and LDL-c; HDL-c was dropped. Serum FSH, LH, and testosterone values declined. A significant disorder in expression levels of genes regulating the hypothalamic-pituitary-testicular-axis pathway. Hypothalamic GnRH, Kisspeptin-1, Kisspeptin-r1, and Adipo-R1 values declined. GnIH and Leptin-R1 values raised up. Pituitary GnRH-R values declined. Testicular tissue STAR, HSD17B3, and CYP19A1 values declined. Adipose tissue adiponectin declined, while leptin raised up. CMC-SPIONs 25-50 mg could modulate the deranged biochemical parameters and correct the deranged expression levels of all previous genes. Co-treatments revealed highly synergistic effects on all parameters. Overall, CMC-SPIONs have significant efficiency whether alone or with Orlisat in limiting obesity and consequence subfertility. Conclusion: CMC-SPIONs act as an incoming promising contender for obesity and MOSH disorders management, and need more studies on their mechanisms.


Asunto(s)
Hipogonadismo , Obesidad , Enfermedades de los Roedores , Ratas , Masculino , Animales , Leptina/metabolismo , Leptina/uso terapéutico , Orlistat/metabolismo , Orlistat/farmacología , Orlistat/uso terapéutico , Testículo/metabolismo , Obesidad/genética , Obesidad/metabolismo , Obesidad/veterinaria , Hipogonadismo/metabolismo , Hipogonadismo/veterinaria , Hipotálamo/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/uso terapéutico , Nanopartículas Magnéticas de Óxido de Hierro
3.
Front Endocrinol (Lausanne) ; 15: 1343738, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633754

RESUMEN

Background: Glycine is an integral component of the human detoxification system as it reacts with potentially toxic exogenous and endogenously produced compounds and metabolites via the glycine conjugation pathway for urinary excretion. Because individuals with obesity have reduced glycine availability, this detoxification pathway may be compromised. However, it should be restored after bariatric surgery because of increased glycine production. Objective: To examine the impact of obesity-associated glycine deficiency on the glycine conjugation pathway. We hypothesize that the synthesis rates of acylglycines from endogenous and exogenous sources are significantly reduced in individuals with obesity but increase after bariatric surgery. Methods: We recruited 21 participants with class III obesity and 21 with healthy weight as controls. At baseline, [1,2-13C2] glycine was infused to study the glycine conjugation pathway by quantifying the synthesis rates of several acylglycines. The same measurements were repeated in participants with obesity six months after bariatric surgery. Data are presented as mean ± standard deviation, and p-value< 0.05 is considered statistically significant. Results: Baseline data of 20 participants with obesity were first compared to controls. Participants with obesity were significantly heavier than controls (mean BMI 40.5 ± 7.1 vs. 20.8 ± 2.1 kg/m2). They had significantly lower plasma glycine concentration (168 ± 30 vs. 209 ± 50 µmol/L) and slower absolute synthesis rates of acetylglycine, isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine. Pre- and post-surgery data were available for 16 participants with obesity. Post-surgery BMI decreased from 40.9 ± 7.3 to 31.6 ± 6.0 kg/m2. Plasma glycine concentration increased from 164 ± 26 to 212 ± 38 µmol/L) and was associated with significantly higher rates of excretion of acetylglycine, isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine. Benzoic acid (a xenobiotic dicarboxylic acid) is excreted as benzoylglycine; its synthesis rate was significantly slower in participants with obesity but increased after bariatric surgery. Conclusion: Obesity-associated glycine deficiency impairs the human body's ability to eliminate endogenous and exogenous metabolites/compounds via the glycine conjugation pathway. This impairment is ameliorated when glycine supply is restored after bariatric surgery. These findings imply that dietary glycine supplementation could treat obesity-associated metabolic complications due to the accumulation of intramitochondrial toxic metabolites. Clinical trial registration: https://clinicaltrials.gov/study/NCT04660513, identifier NCT04660513.


Asunto(s)
Cirugía Bariátrica , Ácido Benzoico , Humanos , Ácido Benzoico/metabolismo , Glicina , Hipuratos/metabolismo , Obesidad , Estudios de Casos y Controles
4.
J Diabetes ; 16(4): e13541, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38599822

RESUMEN

Kisspeptins (KPs) are proteins that were first recognized to have antimetastatic action. Later, the critical role of this peptide in the regulation of reproduction was proved. In recent years, evidence has been accumulated supporting a role for KPs in regulating metabolic processes in a sexual dimorphic manner. It has been proposed that KPs regulate metabolism both indirectly via gonadal hormones and/or directly via the kisspeptin receptor in the brain, brown adipose tissue, and pancreas. The aim of the review is to provide both experimental and clinical evidence indicating that KPs are peptides linking metabolism and reproduction. We propose that KPs could be used as a potential target to treat both metabolic and reproductive abnormalities. Thus, we focus on the consequences of disruptions in KPs and their receptors in metabolic conditions such as diabetes, undernutrition, obesity, and reproductive disorders (hypogonadotropic hypogonadism and polycystic ovary syndrome). Data from both animal models and human subjects indicate that alterations in KPs in the case of metabolic imbalance lead also to disruptions in reproductive functions. Changes both in the hypothalamic and peripheral KP systems in animal models of the aforementioned disorders are discussed. Finally, an overview of current clinical studies involving KP in fertility and metabolism show fewer studies on metabolism (15%) and only one to date on both. Presented data indicate a dynamic and emerging field of KP studies as possible therapeutic targets in treatments of both reproductive and metabolic dysfunctions.


Asunto(s)
Kisspeptinas , Reproducción , Animales , Femenino , Humanos , Kisspeptinas/metabolismo , Hipotálamo/metabolismo , Obesidad/metabolismo , Péptidos
5.
Zebrafish ; 21(2): 223-230, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38621217

RESUMEN

Obesity is a public health concern resulting in a variety of health complications, including heart disease and insulin resistance. Estrogens have been associated with a reduced risk of obesity, but this relationship remains incompletely understood. We assessed the role of 17ß-estradiol (E2) in mitigating complications associated with obesity by supplementing E2 in the diets of overfed zebrafish. We report that dietary E2 supplementation protects against weight gain and modulates de novo cholesterol synthesis in a sex-specific manner. Our studies lead us to propose a model in which E2 regulates hmgcr expression independently of unsaturated fat consumption. These data can be used to develop sex-specific treatments for obesity-related health conditions.


Asunto(s)
Grasas Insaturadas , Pez Cebra , Masculino , Femenino , Animales , Pez Cebra/metabolismo , Grasas Insaturadas/metabolismo , Estradiol/farmacología , Estradiol/metabolismo , Estrógenos/metabolismo , Obesidad/etiología , Colesterol/metabolismo , Suplementos Dietéticos
6.
Zhongguo Zhen Jiu ; 44(4): 449-454, 2024 Apr 12.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38621733

RESUMEN

OBJECTIVES: To observe the effects of moxibustion on intestinal barrier function and Toll-like receptor 4 (TLR4)/nuclear factor-κB p65 (NF-κB p65) signaling pathway in obese rats and explore the mechanism of moxibustion in the intervention of obesity. METHODS: Fifty-five Wistar rats of SPF grade were randomly divided into a normal group (10 rats) and a modeling group (45 rats). In the modeling group, the obesity model was established by feeding high-fat diet. Thirty successfully-modeled rats were randomized into a model group, a moxibustion group, and a placebo-control group, with 10 rats in each one. In the moxibustion group, moxibustion was applied at the site 3 cm to 5 cm far from the surface of "Zhongwan" (CV 12), with the temperature maintained at (46±1 ) ℃. In the placebo-control group, moxibustion was applied at the site 8 cm to 10 cm far from "Zhongwan" (CV 12), with the temperature maintained at (38±1) ℃. The intervention was delivered once daily for 8 weeks in the above two groups. The body mass and food intake of the rats were observed before and after intervention in each group. Using ELISA methool, the levels of serum triacylglycerol (TG), total cholesterol (TC) and lipopolysaccharide (LPS) were detected and the insulin resistance index (HOMA-IR) was calculated. HE staining was used to observe the morphology of colon tissue. The mRNA expression of zonula occludens-1 (ZO-1), Occludin, Claudin-1, TLR4 and NF-κB p65 in the colon tissue was detected by quantitative real-time PCR; and the protein expression of ZO-1, Occludin, Claudin-1, TLR4 and NF-κB p65 was detected by Western blot in the rats of each group. RESULTS: Compared with the normal group, the body mass, food intake, the level of HOMA-IR, and the serum levels of TC, TG and LPS were increased in the rats of the model group (P<0.01); those indexes in the moxibustion group were all reduced when compared with the model group and the placebo-control group respectively (P<0.01, P<0.05). Compared with the normal group, a large number of epithelial cells in the mucosa of colon tissue was damaged, shed, and the inflammatory cells were infiltrated obviously in the interstitium in the rats of the model group. When compared with the model group, in the moxibustion group, the damage of the colon tissue was recovered to various degrees and there were few infiltrated inflammatory cells in the interstitium, while, the epithelial injury of the colon tissue was slightly recovered and the infiltrated inflammatory cells in the interstitium were still seen in the placebo-control group. The mRNA and protein expressions of ZO-1, Occludin and Caudin-1 were decreased in the model group compared with those in the normal group (P<0.01). When compared with the model group and the placebo-control group, the mRNA and protein expressions of these indexes were increased in the moxibustion group (P<0.01, P<0.05). In the model group, the mRNA and protein expressions of TLR4 and NF-κB p65 were increased when compared with those in the normal group (P<0.01), and the mRNA and protein expressions of these indexes were reduced in the moxibustion group when compared with those in the model group and the placebo-control group (P<0.01). CONCLUSIONS: Moxibustion can reduce the body mass and food intake, regulate the blood lipid and improve insulin resistance in the rats of obesity. It may be related to alleviating inflammatory response through improving intestinal barrier function and modulating the intestinal TLR4/NF-κB p65 signaling pathway.


Asunto(s)
Resistencia a la Insulina , Moxibustión , Ratas , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Ratas Wistar , Receptor Toll-Like 4/genética , Lipopolisacáridos/metabolismo , Funcion de la Barrera Intestinal , Ocludina/metabolismo , Claudina-1/metabolismo , Transducción de Señal , Obesidad/genética , Obesidad/terapia , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
7.
Gynecol Endocrinol ; 40(1): 2341701, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38622970

RESUMEN

OBJECTIVE: To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients. METHODS: This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated. RESULTS: ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease. CONCLUSION: ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.


Asunto(s)
Diabetes Mellitus , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Síndrome del Ovario Poliquístico , Ácido Tióctico , Femenino , Humanos , Insulina , Resistencia a la Insulina/fisiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Estudios Retrospectivos , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico
8.
Food Funct ; 15(8): 4475-4489, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38563737

RESUMEN

The objective of this study was to investigate the anti-obesity effects and underlying mechanism of Lacticaseibacillus rhamnosus HF01 fermented yogurt (HF01-Y). Herein, obesity was induced in mice through a high-fat diet and the changes in the gut microbiota were evaluated using 16S rRNA gene sequencing, combined with the expression levels of the liver AMPK signaling pathway to analyze the potential relationship between HF01-Y-mediated gut microbiota and obesity. The results showed that supplementation with HF01-Y improved obesity-related phenotypes in mice, including reduced body weight, improved serum lipid profiles, and decreased hepatic lipid droplet formation. In addition, HF01-Y altered the composition of the gut microbiota in obese mice, significantly upregulated norank_f__Muribaculaceae, unclassified_c__Clostridia, Blautia, unclassified_o__Bacteroidales, and Rikenellaceae_RC9_gut_group, while downregulating unclassified_f__Desulfovibrionaceae, Colidextribacter, and unclassified_f__Oscillospiraceae. These alterations led to an increase of the cecum butyric acid content, which in turn indirectly promoted the activation of the AMPK signaling pathway, subsequently, inhibited fat synthesis, and promoted fatty acid oxidation related gene expression. Therefore, HF01-Y was likely to alleviate hepatic fat and relieve obesity by modulating the gut microbiota-butyric acid-hepatic lipid metabolism axis, ultimately promoting host health.


Asunto(s)
Ácido Butírico , Dieta Alta en Grasa , Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Obesidad , Yogur , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Masculino , Metabolismo de los Lípidos/efectos de los fármacos , Yogur/microbiología , Obesidad/metabolismo , Obesidad/dietoterapia , Obesidad/microbiología , Ácido Butírico/metabolismo , Hígado/metabolismo , Hígado Graso/metabolismo , Fermentación , Humanos , Probióticos/farmacología
9.
Food Funct ; 15(8): 4515-4526, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38567805

RESUMEN

Guanidinoacetic acid (GAA) is a naturally occurring amino acid derivative that plays a critical role in energy metabolism. In recent years, a growing body of evidence has emerged supporting the importance of GAA in metabolic dysfunction. Hence, we aimed to investigate the effects of GAA on hepatic and adipose tissue metabolism, as well as systemic inflammatory responses in obese middle-aged mice models and attempted to explore the underlying mechanism. We found that dietary supplementation of GAA inhibited inguinal white adipose tissue (iWAT) hypertrophy in high-fat diet (HFD)-fed mice. In addition, GAA supplementation observably decreased the levels of some systemic inflammatory factors, including IL-4, TNF-α, IL-1ß, and IL-6. Intriguingly, GAA supplementation ameliorated hepatic steatosis and lipid deposition in HFD-fed mice, which was revealed by decreased levels of TG, TC, LDL-C, PPARγ, SREBP-1c, FASN, ACC, FABP1, and APOB and increased levels of HDL-C in the liver. Moreover, GAA supplementation increased the expression of browning markers and mitochondrial-related genes in the iWAT. Further investigation showed that dietary GAA promoted the browning of the iWAT via activating the AMPK/Sirt1 signaling pathway and might be associated with futile creatine cycling in obese mice. These results indicate that GAA has the potential to be used as an effective ingredient in dietary interventions and thus may play an important role in ameliorating and preventing HFD-induced obesity and related metabolic diseases.


Asunto(s)
Tejido Adiposo Pardo , Tejido Adiposo Blanco , Dieta Alta en Grasa , Glicina , Glicina/análogos & derivados , Inflamación , Ratones Endogámicos C57BL , Obesidad , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Masculino , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Glicina/farmacología , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Inflamación/tratamiento farmacológico , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Suplementos Dietéticos
10.
BMC Vet Res ; 20(1): 133, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570815

RESUMEN

BACKGROUND: Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. RESULTS: After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. CONCLUSIONS: 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.


Asunto(s)
Diabetes Mellitus , Enfermedades de los Perros , Microbioma Gastrointestinal , Enfermedades Metabólicas , Morus , Humanos , Animales , Perros , 1-Desoxinojirimicina/farmacología , Extractos Vegetales/farmacología , Obesidad/tratamiento farmacológico , Obesidad/veterinaria , Diabetes Mellitus/veterinaria , Enfermedades Metabólicas/veterinaria , Hojas de la Planta
12.
JAMA Netw Open ; 7(4): e244855, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38573637

RESUMEN

Importance: Perceived social isolation is associated with negative health outcomes, including increased risk for altered eating behaviors, obesity, and psychological symptoms. However, the underlying neural mechanisms of these pathways are unknown. Objective: To investigate the association of perceived social isolation with brain reactivity to food cues, altered eating behaviors, obesity, and mental health symptoms. Design, Setting, and Participants: This cross-sectional, single-center study recruited healthy, premenopausal female participants from the Los Angeles, California, community from September 7, 2021, through February 27, 2023. Exposure: Participants underwent functional magnetic resonance imaging while performing a food cue viewing task. Main Outcomes and Measures: The main outcomes included brain reactivity to food cues, body composition, self-reported eating behaviors (food cravings, reward-based eating, food addiction, and maladaptive eating behaviors), and mental health symptoms (anxiety, depression, positive and negative affect, and psychological resilience). Results: The study included 93 participants (mean [SD] age, 25.38 [7.07] years). Participants with higher perceived social isolation reported higher fat mass percentage, lower diet quality, increased maladaptive eating behaviors (cravings, reward-based eating, uncontrolled eating, and food addiction), and poor mental health (anxiety, depression, and psychological resilience). In whole-brain comparisons, the higher social isolation group showed altered brain reactivity to food cues in regions of the default mode, executive control, and visual attention networks. Isolation-related neural changes in response to sweet foods correlated with various altered eating behaviors and psychological symptoms. These altered brain responses mediated the connection between social isolation and maladaptive eating behaviors (ß for indirect effect, 0.111; 95% CI, 0.013-0.210; P = .03), increased body fat composition (ß, -0.141; 95% CI, -0.260 to -0.021; P = .02), and diminished positive affect (ß, -0.089; 95% CI, -0.188 to 0.011; P = .09). Conclusions and Relevance: These findings suggest that social isolation is associated with altered neural reactivity to food cues within specific brain regions responsible for processing internal appetite-related states and compromised executive control and attentional bias and motivation toward external food cues. These neural responses toward specific foods were associated with an increased risk for higher body fat composition, worsened maladaptive eating behaviors, and compromised mental health. These findings underscore the need for holistic mind-body-directed interventions that may mitigate the adverse health consequences of social isolation.


Asunto(s)
Señales (Psicología) , Salud Mental , Femenino , Humanos , Adulto , Estudios Transversales , Encéfalo/diagnóstico por imagen , Aislamiento Social , Conducta Alimentaria , Obesidad
13.
Front Endocrinol (Lausanne) ; 15: 1344262, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38559696

RESUMEN

Obesity, a multifactorial disease with many complications, has become a global epidemic. Weight management, including dietary supplementation, has been confirmed to provide relevant health benefits. However, experimental evidence and mechanistic elucidation of dietary supplements in this regard are limited. Here, the weight loss efficacy of MHP, a commercial solid beverage consisting of mulberry leaf aqueous extract and Hippophae protein peptides, was evaluated in a high-fat high-fructose (HFF) diet-induced rat model of obesity. Body component analysis and histopathologic examination confirmed that MHP was effective to facilitate weight loss and adiposity decrease. Pathway enrichment analysis with differential metabolites generated by serum metabolomic profiling suggests that PPAR signal pathway was significantly altered when the rats were challenged by HFF diet but it was rectified after MHP intervention. RNA-Seq based transcriptome data also indicates that MHP intervention rectified the alterations of white adipose tissue mRNA expressions in HFF-induced obese rats. Integrated omics reveals that the efficacy of MHP against obesogenic adipogenesis was potentially associated with its regulation of PPARγ and FGFR1 signaling pathway. Collectively, our findings suggest that MHP could improve obesity, providing an insight into the use of MHP in body weight management.


Asunto(s)
Hippophae , Morus , Ratas , Animales , PPAR gamma/genética , PPAR gamma/metabolismo , Hippophae/metabolismo , Morus/metabolismo , Dieta Alta en Grasa/efectos adversos , Obesidad/metabolismo , Tejido Adiposo Blanco/metabolismo , Transducción de Señal , Pérdida de Peso
14.
J Nat Med ; 78(3): 576-589, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38662301

RESUMEN

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.


Asunto(s)
Envejecimiento , Dieta Alta en Grasa , Medicamentos Herbarios Chinos , Obesidad , Animales , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Ratones , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Masculino , Dieta Alta en Grasa/efectos adversos , Envejecimiento/efectos de los fármacos , Humanos , Células Hep G2 , Ratones Endogámicos C57BL , Proteína Desacopladora 1/metabolismo , Triglicéridos/sangre , Triglicéridos/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Aspartato Aminotransferasas/sangre
15.
Biosci Rep ; 44(4)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38577975

RESUMEN

Since 1975, the incidence of obesity has increased to epidemic proportions, and the number of patients with obesity has quadrupled. Obesity is a major risk factor for developing other serious diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Recent epidemiologic studies have defined obesity as a risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease (AD) and other types of dementia. Despite all these serious comorbidities associated with obesity, there is still a lack of effective antiobesity treatment. Promising candidates for the treatment of obesity are anorexigenic neuropeptides, which are peptides produced by neurons in brain areas implicated in food intake regulation, such as the hypothalamus or the brainstem. These peptides efficiently reduce food intake and body weight. Moreover, because of the proven interconnection between obesity and the risk of developing AD, the potential neuroprotective effects of these two agents in animal models of neurodegeneration have been examined. The objective of this review was to explore anorexigenic neuropeptides produced and acting within the brain, emphasizing their potential not only for the treatment of obesity but also for the treatment of neurodegenerative disorders.


Asunto(s)
Fármacos Antiobesidad , Neuropéptidos , Fármacos Neuroprotectores , Obesidad , Humanos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Animales , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Neuropéptidos/metabolismo , Neuropéptidos/farmacología , Neuropéptidos/uso terapéutico , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/prevención & control , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Hipotálamo/patología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/prevención & control , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Ingestión de Alimentos/efectos de los fármacos
16.
Food Funct ; 15(8): 4627-4641, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38592736

RESUMEN

Diet-induced thermogenesis (DIT) is crucial for maintaining body weight homeostasis, and the role of dietary fatty acids in modulating DIT is essential. However, the underlying mechanism of fatty acid regulated diet-induced thermogenesis remains elusive. Utilizing the diet- and genetic ablation-induced obese mice models, we found that the C16 unsaturated fatty acids, trans-palmitoleic acid (TPA) and cis-palmitoleic acid (CPA), significantly increased the energy expenditure by promoting the thermogenesis of brown adipose tissues and the production of beige cells in white adipose. As a result, there is a significant reduction in the occurrence of obesity, associated hepatic steatosis and hyperglycemia. Notably, TPA exhibited more potent effects on promoting DIT and alleviating obesity than CPA did. Using inhibitor and gene deletion mice models, we unveiled that TPA acted as a signaling molecule to play a biological function, which could be sensed by the hypothalamic FFAR1 to activate the sympathetic nervous system in promoting adipose tissue thermogenesis. Together, these results demonstrate the underlying mechanism of free fatty acids associated-DIT and will provide fresh insights into the roles of trans-fatty acids in the development of obesity.


Asunto(s)
Ácidos Grasos Monoinsaturados , Hipotálamo , Ratones Endogámicos C57BL , Obesidad , Receptores Acoplados a Proteínas G , Transducción de Señal , Termogénesis , Animales , Termogénesis/efectos de los fármacos , Ratones , Obesidad/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Ácidos Grasos Monoinsaturados/farmacología , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Dieta Alta en Grasa
17.
Adv Mater ; 36(21): e2310351, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38591658

RESUMEN

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.


Asunto(s)
Enfermedades Metabólicas , Obesidad , Animales , Obesidad/metabolismo , Obesidad/terapia , Ratones , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/terapia , Enfermedades Metabólicas/tratamiento farmacológico , Eje Cerebro-Intestino , Titanio/química , Capsaicina/farmacología , Capsaicina/administración & dosificación , Administración Oral , Terapia por Estimulación Eléctrica/métodos , Ratones Endogámicos C57BL , Masculino , Compuestos de Bario
18.
Contemp Clin Trials ; 141: 107523, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38608752

RESUMEN

INTRODUCTION: Intensive weight management programs are effective but often have low enrollment and high attrition. Lack of motivation is a key psychological barrier to enrollment, engagement, and weight loss. Mental Contrasting with Implementation Intentions (MCII) is a unique imagery technique that increases motivation for behavior change. We describe our study protocol to assess the efficacy and implementation of MCII to enhance the effectiveness of VA's MOVE! or TeleMOVE! weight management programs using a procedure called "WOOP" (Wish, Outcome, Obstacle, Plan) for Veterans. We hypothesize that WOOP+MOVE! or TeleMOVE! (intervention) will lead to greater MOVE!/TeleMOVE! program engagment and consequently weight loss than MOVE!/TeleMOVE! alone (control). METHOD: Veterans are randomized to either the intervention or control. Both arms receive the either MOVE! or TeleMOVE! weight management programs. The intervention group receives an hour long WOOP training while the control group receives patient education. Both groups receive telephone follow up calls at 3 days, 4 weeks, and 2 months post-baseline. Eligible participants are Veterans (ages 18-70 years) with either obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 25 kg/m2) and an obesity-associated co-morbidity. At baseline, 6 and 12 months, we assess weight, diet, physical activity in both groups. The primary outcome is mean percent weight change at 6 months. Secondary outcomes include changes in waist circumference, diet, physical activity, and dieting self-efficacy and engagement in regular physical activity. We assess implementation using the RE-AIM framework. CONCLUSION: If WOOP VA is found to be efficacious, it will be an important tool to facilitate weight management and improve weight outcomes. CLINICAL TRIAL REGISTRATION: NCT05014984.


Asunto(s)
Intención , Motivación , Veteranos , Programas de Reducción de Peso , Humanos , Programas de Reducción de Peso/métodos , Programas de Reducción de Peso/organización & administración , Estudios Prospectivos , Veteranos/psicología , Ejercicio Físico , Pérdida de Peso , Persona de Mediana Edad , Masculino , Femenino , Adulto , Obesidad/terapia , Estados Unidos , Educación del Paciente como Asunto/métodos , Educación del Paciente como Asunto/organización & administración , Anciano , United States Department of Veterans Affairs , Índice de Masa Corporal
19.
PLoS One ; 19(4): e0300544, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38656972

RESUMEN

Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target GLP-1 receptors have recently come to the market. Here, we describe the effects of tesofensine, a novel anti-obesity drug that acts as a triple monoamine neurotransmitter reuptake inhibitor. Using various techniques, we investigated its effects on weight loss and underlying neuronal mechanisms in mice and rats. These include behavioral tasks, DeepLabCut videotaped analysis, electrophysiological ensemble recordings, optogenetic activation, and chemogenetic silencing of GABAergic neurons in the Lateral Hypothalamus (LH). We found that tesofensine induces a greater weight loss in obese rats than lean rats, while differentially modulating the neuronal ensembles and population activity in LH. In Vgat-ChR2 and Vgat-IRES-cre transgenic mice, we found for the first time that tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior, and chemogenetically silencing them enhanced tesofensine's food-suppressing effects. Unlike phentermine, a dopaminergic appetite suppressant, tesofensine causes few, if any, head-weaving stereotypy at therapeutic doses. Most importantly, we found that tesofensine prolonged the weight loss induced by 5-HTP, a serotonin precursor, and blocked the body weight rebound that often occurs after weight loss. Behavioral studies on rats with the tastant sucrose indicated that tesofensine's appetite suppressant effects are independent of taste aversion and do not directly affect the perception of sweetness or palatability of sucrose. In summary, our data provide new insights into the effects of tesofensine on weight loss and the underlying neuronal mechanisms, suggesting that tesofensine may be an effective treatment for obesity and that it may be a valuable adjunct to other appetite suppressants to prevent body weight rebound.


Asunto(s)
Fármacos Antiobesidad , Compuestos Bicíclicos Heterocíclicos con Puentes , Neuronas GABAérgicas , Obesidad , Animales , Neuronas GABAérgicas/efectos de los fármacos , Neuronas GABAérgicas/metabolismo , Ratas , Ratones , Fármacos Antiobesidad/farmacología , Masculino , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Conducta Alimentaria/efectos de los fármacos , Área Hipotalámica Lateral/efectos de los fármacos , Área Hipotalámica Lateral/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Ratones Transgénicos , Pérdida de Peso/efectos de los fármacos , Ratas Sprague-Dawley
20.
Nat Commun ; 15(1): 3443, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658557

RESUMEN

The hypothalamus contains a remarkable diversity of neurons that orchestrate behavioural and metabolic outputs in a highly plastic manner. Neuronal diversity is key to enabling hypothalamic functions and, according to the neuroscience dogma, it is predetermined during embryonic life. Here, by combining lineage tracing of hypothalamic pro-opiomelanocortin (Pomc) neurons with single-cell profiling approaches in adult male mice, we uncovered subpopulations of 'Ghost' neurons endowed with atypical molecular and functional identity. Compared to 'classical' Pomc neurons, Ghost neurons exhibit negligible Pomc expression and are 'invisible' to available neuroanatomical approaches and promoter-based reporter mice for studying Pomc biology. Ghost neuron numbers augment in diet-induced obese mice, independent of neurogenesis or cell death, but weight loss can reverse this shift. Our work challenges the notion of fixed, developmentally programmed neuronal identities in the mature hypothalamus and highlight the ability of specialised neurons to reversibly adapt their functional identity to adult-onset obesogenic stimuli.


Asunto(s)
Hipotálamo , Neuronas , Obesidad , Proopiomelanocortina , Análisis de la Célula Individual , Animales , Proopiomelanocortina/metabolismo , Proopiomelanocortina/genética , Neuronas/metabolismo , Obesidad/metabolismo , Obesidad/patología , Masculino , Ratones , Hipotálamo/metabolismo , Hipotálamo/citología , Modelos Animales de Enfermedad , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Ratones Transgénicos , Neurogénesis , Ratones Obesos
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