Obesity Weight Gain Research Articles

Transcriptomic (DNA Microarray) and Metabolome (LC-TOF-MS) Analyses of the Liver in High-Fat Diet Mice after Intranasal Administration of GALP (Galanin-like Peptide).

The aim of this research was to test the efficacy and potential clinical application of intranasal administration of galanin-like peptide (GALP) as an anti-obesity treatment under the hypothesis that GALP prevents obesity in mice fed a high-fat diet (HFD). Focusing on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system, we confirmed that, compared with a control (saline), intranasally administered GALP prevented further body weight gain in diet-induced obesity (DIO) mice with continued access to an HFD. Using an omics-based approach, we identified several genes and metabolites in the liver tissue of DIO mice that were altered by the administration of intranasal GALP. We used whole-genome DNA microarray and metabolomics analyses to determine the anti-obesity effects of intranasal GALP in DIO mice fed an HFD. Transcriptomic profiling revealed the upregulation of flavin-containing dimethylaniline monooxygenase 3 (Fmo3), metallothionein 1 and 2 (Mt1 and Mt2, respectively), and the Aldh1a3, Defa3, and Defa20 genes. Analysis using the DAVID tool showed that intranasal GALP enhanced gene expression related to fatty acid elongation and unsaturated fatty acid synthesis and downregulated gene expression related to lipid and cholesterol synthesis, fat absorption, bile uptake, and excretion. Metabolite analysis revealed increased levels of coenzyme Q10 and oleoylethanolamide in the liver tissue, increased levels of deoxycholic acid (DCA) and taurocholic acid (TCA) in the bile acids, increased levels of taurochenodeoxycholic acid (TCDCA), and decreased levels of ursodeoxycholic acid (UDCA). In conclusion, intranasal GALP administration alleviated weight gain in obese mice fed an HFD via mechanisms involving antioxidant, anti-inflammatory, and fatty acid metabolism effects and genetic alterations. The gene expression data are publicly available at NCBI GSE243376.

Dietary Folic Acid Supplementation Inhibits HighFat DietInduced Body Weight Gain through Gut Microbiota-Associated Branched-Chain Amino Acids and Mitochondria in Mice.

The effects of folic acid on body weight gain in obesity and gut microbiota-associated branched-chain amino acids (BCAAs) and mitochondrial function were investigated. Three- to four-wk-old male C57BL/6J conventional (CV) and germ-free (GF) mice were fed a high-fat diet (HD), folic acid-supplemented HD (FSHD) and a normal-fat diet (ND) for 25 wk. In CV mice, the HD-induced increases in body weight and plasma BCAA concentrations, downregulated expression of genes related to BCAA catabolism (Bcat2, Bckdha, or Ppm1k), mitochondrial biogenesis (Pgc-1α, Cox1, Nd1 or Nd6), fusion (Mfn1, Mfn2 or Opa1) and mitophagy (Pink1 or Park2), and upregulated expression of the fission-associated gene Drp1 in epididymal fat were reversely corrected with FSHD feeding. In contrast, the expression of these genes in the liver was the opposite under HD feeding or folic acid supplementation. In GF mice, plasma BCAA concentrations were much less affected by HD feeding and were reduced by FSHD feeding, with almost no alterations in the expression of genes associated with BCAA catabolism and mitochondrial function. Further analysis indicated a correlation between adipose and hepatic Mt C/N and plasma BCAA concentrations, and the latter had a close association with specific gut bacteria. Therefore, dietary folic acid supplementation differentially affected body weight gain, BCAA catabolism, and mitochondrial dynamics and metabolism under HD feeding between CV and GF mice, suggesting that gut bacteria-altered BCAAs and mitochondria might partially share the responsibility for the beneficial effects of dietary folic acid on obesity.

Methionine enkephalin promotes white fat browning through cAMP/PKA pathway

AimsObesity and its related metabolic disorders, including insulin resistance and fatty liver, have become a serious global public health problem. Previous studies have shown Methionine Enkephalin (MetEnk) has the potential on adipocyte browning, however, its effects on the potential mechanisms of its regulation in browning as well as its improvement in energy metabolic homeostasis remain to be deciphered. Main methodsC57BL/6J male mice were fed with high-fat diet (HFD) to induce obesity model, and MetEnk was injected subcutaneously to detect changes in the metabolic status of mice, adipocytes and HepG2 cells were also treated with MetEnk, and transcriptomic, metabolomic were used to detect the changes of lipid metabolism, mitochondrial function, inflammation and other related factors. Key findingsWe found that MetEnk effectively protected against obesity weight gain in HFD-induced C57BL/6J mice, significantly improved glucose tolerance and insulin sensitivity, reduced the expression levels of interleukin 6 (IL-6), promoted white fat browning, moreover, using a combination of transcriptomic, metabolomic and inhibitors, it was found that MetEnk improved mitochondrial function, promoted thermogenesis and lipolysis by activating cAMP/PKA pathway in adipocytes, further analysis found that MetEnk also promoted lipolysis and alleviated inflammation through AMP-activated protein kinase (AMPK) pathway in mice liver and HepG2 cells. SignificanceOur study provides profound evidence for the role of MetEnk in improving lipid metabolism disorders. This study provides a mechanical foundation for investigating the potential of MetEnk to improve obesity and its associated metabolic disorders.

Gestational Weight Gain in Patients With Obesity and Diabetes: A Comparison of 2009 Institute of Medicine Versus 2019 JAMA Recommendations [A270

INTRODUCTION: Excessive gestational weight gain (GWG) is associated with adverse maternal and neonatal outcomes. Current guidelines established by the United States' Institute of Medicine (IOM) in 2009 recommend GWG of 11–20 lb for all obese patients. In 2019, a JAMA meta-analysis proposed recommending less weight gain in obesity (0–13 lb), not accounting for pre-existing maternal co-morbidities. We aim to ascertain whether, in obese diabetic pregnancies, GWG within the updated JAMA guidelines is associated with better outcomes. METHODS: IRB approval was obtained. Using a large urban hospital's de-identified obstetric database, obese diabetic patients from 2011 to 2020 were categorized into two groups: IOM and JAMA, depending on their GWG. Diagnosis codes were used to assess outcomes. Chi-square test, independent samples T-test, and Wilcoxon rank-sum test were used. RESULTS: Of 240 patients with obesity and diabetes, 135 fell within IOM weight gain guidelines and 65 within JAMA. The groups were not significantly different in age, BMI, A1C, or proportion with prior cesarean delivery. For maternal outcomes, chronic hypertension was independently associated with weight gain within the JAMA guidelines versus IOM (55% vs. 36%, P=.0082). There were no significant differences in rates of cesarean delivery (P=.73) or pre-eclampsia (P=.92). For neonatal outcomes, no differences were noted in NICU admission (P=.73), macrosomia (P=.72), or preterm delivery (P=.21) rates. CONCLUSION: For women with obesity and diabetes, chronic hypertension was associated with marginally less weight gain. Further research may be needed before clinicians advise the stricter GWG recommendations in the new JAMA guidelines rather than the current standard of IOM guidelines.

Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis

Altered methionine metabolism is associated with weight gain in obesity. The methionine adenosyltransferase (MAT), catalyzing the first reaction of the methionine cycle, plays an important role regulating lipid metabolism. However, its role in obesity, when a plethora of metabolic diseases occurs, is still unknown. By using antisense oligonucleotides (ASO) and genetic depletion of Mat1a, here, we demonstrate that Mat1a deficiency in diet-induce obese or genetically obese mice prevented and reversed obesity and obesity-associated insulin resistance and hepatosteatosis by increasing energy expenditure in a hepatocyte FGF21 dependent fashion. The increased NRF2-mediated FGF21 secretion induced by targeting Mat1a, mobilized plasma lipids towards the BAT to be catabolized, induced thermogenesis and reduced body weight, inhibiting hepatic de novo lipogenesis. The beneficial effects of Mat1a ASO were abolished following FGF21 depletion in hepatocytes. Thus, targeting Mat1a activates the liver-BAT axis by increasing NRF2-mediated FGF21 secretion, which prevents obesity, insulin resistance and hepatosteatosis.

О роли кишечных бактерий в физиологической регуляции аппетита и энергетического обмена

The current “homeostatic theory” of appetite regulation assumes that alternation of hunger and satiety depends on energy balance in the host tissues encoded and transmitted to the brain by neuronal and hormonal signals. However, relatively low metabolic activity of fat tissue cannot explain short-term regulation of appetite. In this paper, I am presenting the evidence supporting bacterial contribution to the appetite regulation by showing that energy metabolism of gut bacteria can be linked to the host appetite cycles. Indeed, the daily metabolic activity of gut bacteria (~2 kcal/g) is about 100 times higher than that of the human body. Importantly, the reproduction cycle of gut bacteria, which is independently regulated from the host, is temporally identical to the short-term changes of appetite; 20 min of the bacterial exponential growth duration corresponds to 20 min necessary for physiological satiation. In further support of the “microbial theory”, molecular pathways linking gut bacteria with the host regulation of appetite have been identified. For instance, bacterial caseinolytic protease B (ClpB), whose production increases during the bacterial stationary growth phase, i. e., when the host is satiated, acts as a conformational mimetic of anorexigenic α-melanocyte-stimulating hormone and activates the intestinal satiety pathway. The practical utility to stimulate this pathway and to control body weight gain in obesity was recently validated using ClpB-expressing probiotics. Thus, an important functional contribution of gut bacteria to the host energy metabolism should be considered as a new integral part of the “homeostatic theory” of appetite regulation.

Roles of leptin in the recovery of muscle and bone by reloading after mechanical unloading in high fat diet-fed obese mice

Muscle and bone masses are elevated by the increased mechanical stress associated with body weight gain in obesity. However, the mechanisms by which obesity affects muscle and bone remain unclear. We herein investigated the roles of obesity and humoral factors from adipose tissue in the recovery phase after reloading from disuse-induced muscle wasting and bone loss using normal diet (ND)- or high fat diet (HFD)-fed mice with hindlimb unloading (HU) and subsequent reloading. Obesity did not affect decreases in trabecular bone mineral density (BMD), muscle mass in the lower leg, or grip strength in HU mice. Obesity significantly increased trabecular BMD, muscle mass in the lower leg, and grip strength in reloading mice over those in reloading mice fed ND. Among the humoral factors in epididymal and subcutaneous adipose tissue, leptin mRNA levels were significantly higher in reloading mice fed HFD than in mice fed ND. Moreover, circulating leptin levels were significantly higher in reloading mice fed HFD than in mice fed ND. Leptin mRNA levels in epididymal adipose tissue or serum leptin levels positively correlated with the increases in trabecular BMD, total muscle mass, and grip strength in reloading mice fed ND and HFD. The present study is the first to demonstrate that obesity enhances the recovery of bone and muscle masses as well as strength decreased by disuse after reloading in mice. Leptin may contribute to the recovery of muscle and bone enhanced by obesity in mice.

Difficulties in emotion regulation and deficits in interoceptive awareness in moderate and severe obesity.

Difficulties in emotion regulation and deficits in interoceptive awareness may be responsible for overeating and weight gain in obesity by increasing the risks of problematic eating behaviors. This study aimed to: (1) examine emotion regulation difficulties and interoceptive deficits in obesity; (2) compare the emotion regulation and interoceptive abilities of moderately and severely obese patients. Participants were recruited through the university, diabetology centers and bariatric surgery departments. A total of 165 participants were categorized in three groups, matched by age and gender, according to their Body Mass Index (BMI). The severely obese (SO), moderately obese (MO) and normal weight (NW) groups were constituted of 55 participants each. Self-report questionnaires were used to assess emotion regulation difficulties (CERQ-DERS) and interoceptive awareness (MAIA-FFMQ). Overall, obese participants reported more emotion regulation difficulties and less interoceptive awareness than NW participants did. They also reported a lack of planning strategies and emotional awareness, as well as less ability to observe, notice and trust body sensations. No differences in emotion regulation and interoceptive abilities were found between MO and SO participants. Emotion regulation and interoceptive awareness should be targeted in the psychotherapeutic care of obese people, regardless of their BMI. Level III, case-control analytic study.

Components of the metabolic syndrome are negative predictors of weight loss in obese children with lifestyle intervention

Insulin resistance has been proposed to be associated with weight gain in obesity. Therefore, we analyzed the impact of insulin resistance and its associated cardiovascular risk factors (CRFs) summarized in the Metabolic Syndrome (MetS) on change of weight status in obese children. We analyzed 484 obese children who had participated in a lifestyle intervention and 533 obese children without lifestyle intervention. The changes of BMI-SDS in the time period of 1-year were related to baseline fasting insulin resistance index HOMA, blood pressure, waist circumference, waist-to-height ratio, lipids, uric acid, and HbA1c. In contrast to obese children without lifestyle intervention, BMI-SDS decreased and the majority of CRFs improved significantly in obese children with lifestyle intervention. Age, BMI, waist circumference, waist-to-height ratio, blood pressure, uric acid, triglycerides, and HOMA were negatively significantly related to reduction of BMI-SDS in children with lifestyle intervention. In multiple linear regression analysis adjusted for gender, pubertal stage, and treatment center (R² = 0.26), waist circumference (r = -0.016 [confidence interval -0.019 up to -0.013], p < 0.001) was the strongest negative predictor of weight loss in children with lifestyle intervention. In children without lifestyle intervention, we did not find significant relationships between change of BMI-SDS and CRFs including insulin resistance in multiple regression analysis. Insulin resistance and components of the MetS were associated negatively with weight loss in lifestyle intervention. Waist circumference at baseline was the strongest negative predictor of weight loss suggesting that obese children with abdominal fat distribution need more intensive interventions. This study is registered at clinicaltrials.gov (NCT00435734).

Is there an optimal diet for patients with type 2 diabetes? Yes, the one that works for them!

Diet is fundamental in the aetiology and management of type 2 diabetes. The optimal diet remains unclear and the EASD and ADA have recently adopted increased flexibility with dietary composition, whilst maintaining a focus on reduced energy, reduced saturated fat and increased dietary fibre. This review draws three conclusions on the current evidence for three dietary approaches; high protein diets, very low carbohydrate diets and the Mediterranean diet, specifically for the management of weight, glycaemic control and cardiovascular risk in patients with type 2 diabetes. First, unless energy intake is reduced below energy expenditure over a sustained period of time, weight loss will not occur. Second, weight loss achieved with any dietary approach over the long-term is modest, though compared with the natural history of weight gain in obesity is clinically important. Third, the evidence supports flexibility in dietary composition with no approach superior to another for weight loss, glycaemic control or cardiovascular risk management. Most importantly there is evidence that adherence to any given dietary approach is more important than the macronutrient prescription. So the best diet for those with type 2 diabetes is the one that works for them, and critically the one that they can maintain in the long term.

Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice.

There has been a revolution in cardiovascular neuroscience in recent years with, in some cases, translation into clinical practice of the knowledge of pathophysiology gained through application of sympathetic nerve recording and catecholamine isotope dilution methodology. OBESITY-RELATED HYPERTENSION: An earlier hypothesis, based on findings in most models, was that weight gain in obesity is due in part to sympathetic nervous underactivity reducing thermogenesis. Microneurography and regional noradrenaline spillover measurements in human obesity have disproven this hypothesis, weakening the case for the use of beta3-adrenergic agonists to stimulate thermogenesis. Sympathetic nerve firing rates in post-ganglionic fibres directed to the skeletal muscle vasculature are increased, as is renal sympathetic tone, with a doubling of the spillover rate of noradrenaline from the kidneys. Given these findings, antiadrenergic antihypertensive drugs may be the preferred agents for obesity-related hypertension, but this has not been adequately tested. Whether stress causes high blood pressure, previously hotly debated, has been under recent review by an Australian Government body, the Specialist Medical Review Council. Despite medicolegal implications, the ruling was that stress is one proven cause of hypertension. The judgment was reached after consideration of the epidemiological evidence, but in particular the described neural pathophysiology of essential hypertension: (a) persistent sympathetic nervous stimulation is commonly present, (b) suprabulbar projections of noradrenergic brainstem neurones are activated and (c) adrenaline is released as a cotransmitter in sympathetic nerves. These were taken to be biological markers of stress. At one time, the failing heart was thought to be sympathetically denervated. Longterm administration of inotropic adrenergic agonists, to provide the cardiac catecholamine stimulation thought to be lacking, increased mortality. Noradrenaline isotope dilution methodology subsequently demonstrated that the sympathetic outflow to the heart was preferentially activated, cardiac noradrenaline spillover being increased as much as 50-fold. The level of stimulation of the cardiac sympathetic nerves was the most powerful predictor of death. These observations provide the theoretical foundation for the very successful introduction of beta-adrenergic blockers for treatment of heart failure.