scholarly journals Microglia–Neuron Crosstalk in Obesity: Melodious Interaction or Kiss of Death?

2021 ◽  
Vol 22 (10) ◽  
pp. 5243
Author(s):  
Stéphane Léon ◽  
Agnès Nadjar ◽  
Carmelo Quarta
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Metabolic Disorders ◽  
Body Weight Gain ◽  
Metabolic Stress ◽  
Neuronal Circuits ◽  
Mechanistic Studies ◽  
The Core ◽  
Diet Induced Obesity ◽  
The Brain

Diet-induced obesity can originate from the dysregulated activity of hypothalamic neuronal circuits, which are critical for the regulation of body weight and food intake. The exact mechanisms underlying such neuronal defects are not yet fully understood, but a maladaptive cross-talk between neurons and surrounding microglial is likely to be a contributing factor. Functional and anatomical connections between microglia and hypothalamic neuronal cells are at the core of how the brain orchestrates changes in the body’s metabolic needs. However, such a melodious interaction may become maladaptive in response to prolonged diet-induced metabolic stress, thereby causing overfeeding, body weight gain, and systemic metabolic perturbations. From this perspective, we critically discuss emerging molecular and cellular underpinnings of microglia–neuron communication in the hypothalamic neuronal circuits implicated in energy balance regulation. We explore whether changes in this intercellular dialogue induced by metabolic stress may serve as a protective neuronal mechanism or contribute to disease establishment and progression. Our analysis provides a framework for future mechanistic studies that will facilitate progress into both the etiology and treatments of metabolic disorders.

scholarly journals RIG-I Deficiency Promotes Obesity-Induced Insulin Resistance

2021 ◽  
Vol 14 (11) ◽  
pp. 1178
Author(s):  
Gabsik Yang ◽  
Hye Eun Lee ◽  
Jin Kyung Seok ◽  
Han Chang Kang ◽  
Yong-Yeon Cho ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Er Stress ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Body Weight Gain ◽  
Metabolic Stress ◽  
Normal Diet ◽  
High Fat

Inflammation and immunity are linked to the onset and development of obesity and metabolic disorders. Pattern recognition receptors (PRRs) are key regulators of inflammation and immunity in response to infection and stress, and they have critical roles in metainflammation. In this study, we investigated whether RIG-I (retinoic acid-inducible gene I)-like receptors were involved in the regulation of obesity-induced metabolic stress in RIG-I knockout (KO) mice fed a high-fat diet (HFD). RIG-I KO mice fed an HFD for 12 weeks showed greater body weight gain, higher fat composition, lower lean body mass, and higher epididymal white adipose tissue (eWAT) weight than WT mice fed HFD. In contrast, body weight gain, fat, and lean mass compositions, and eWAT weight of MDA5 (melanoma differentiation-associated protein 5) KO mice fed HFD were similar to those of WT mice fed a normal diet. RIG-I KO mice fed HFD exhibited more severely impaired glucose tolerance and higher HOMA-IR values than WT mice fed HFD. IFN-β expression induced by ER stress inducers, tunicamycin and thapsigargin, was abolished in RIG-I-deficient hepatocytes and macrophages, showing that RIG-I is required for ER stress-induced IFN-β expression. Our results show that RIG-I deficiency promotes obesity and insulin resistance induced by a high-fat diet, presenting a novel role of RIG-I in the development of obesity and metabolic disorders.

scholarly journals The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2441-2452 ◽  
Author(s):  
Tomokazu Hata ◽  
Noriyuki Miyata ◽  
Shu Takakura ◽  
Kazufumi Yoshihara ◽  
Yasunari Asano ◽  
...  
Keyword(s):  
Body Weight ◽  
Anorexia Nervosa ◽  
Weight Gain ◽  
Food Intake ◽  
Brain Stem ◽  
Body Weight Gain ◽  
Field Tests ◽  
Compulsive Behavior ◽  
The Brain ◽  
Poor Weight Gain

Abstract Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.

Extract of Irish potatoes (Solanum tuberosumL.) decreases body weight gain and adiposity and improves glucose control in the mouse model of diet-induced obesity

2014 ◽  
Vol 58 (11) ◽  
pp. 2235-2238 ◽  
Author(s):  
Stan Kubow ◽  
Luc Hobson ◽  
Michèle M. Iskandar ◽  
Kebba Sabally ◽  
Danielle J. Donnelly ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Mouse Model ◽  
Glucose Control ◽  
Body Weight Gain ◽  
Diet Induced Obesity

Capsaicin-sensitive fibers are required for the anorexic action of systemic but not central bombesin

1999 ◽  
Vol 276 (6) ◽  
pp. R1617-R1622 ◽  
Author(s):  
David Michaud ◽  
Hymie Anisman ◽  
Zul Merali
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Neural Circuits ◽  
Body Weight Gain ◽  
Systemic Effects ◽  
Neuronal System ◽  
Afferent Neurons ◽  
The Brain

Bombesin (BN) suppresses food intake in rats whether given centrally or systemically. Although the brain BN-sensitive receptors are known to be essential for the anorexic effect of systemic BN, the mode of communication between the gut and the brain remains unclear. This study assessed whether the anorexic effect of systemic BN is mediated humorally or via neural circuits. Afferent neurons were lesioned using capsaicin (50 mg/kg sc) on postnatal day 2, and responses to BN were assessed during adulthood. Capsaicin treatment decreased body weight gain significantly from postnatal age 4–7 wk. Peripheral BN (4–16 μg/kg ip) dose dependently suppressed food intake in control animals. However, this effect was completely blocked in capsaicin-treated rats. In contrast to systemic effects, feeding-suppressant effects of centrally administered BN (0.01–0.5 μg icv) were not affected by capsaicin treatment. This research suggests that peripheral BN communicates with the brain via a neuronal system(s) whose afferent arm is constituted of capsaicin-sensitive C and/or Aδ-fibers, whereas the efferent arm of this satiety- and/or anorexia-mediating circuitry is capsaicin resistant.

scholarly journals Bauhiniastatin-1 alleviates diet induced obesity and lipid accumulation through modulating PPAR-γ/AMPK expressions: In-vitro, in-vivo and in-silico studies.

2021 ◽  
Author(s):  
Karunakaran Reddy Sankaran ◽  
Lokanatha Oruganti ◽  
Muni Swamy Ganjayi ◽  
Venkataramaiah Chintha ◽  
Muni Kesavulu Muppuru ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Western Blot ◽  
Blot Analysis ◽  
Body Weight Gain ◽  
Liver Lipid ◽  
Ppar Γ ◽  
Diet Induced Obesity

Abstract Background: Consumption of energy dense foods and sedentary lifestyles have led to high prevalence of obesity and associated disorders. Intensive research efforts have focussed to develop effective alternative therapeutics from plant sources. Bauhiniastatins have been reported to possess antineoplastic activity. In the present study, Bauhiniastatin-1 (BSTN1) was isolated and purified from Bauhinia purpurea and evaluated for its therapeutic efficacy against adipogenesis and obesity using high fat diet (HFD)-induced obese rodent model and 3T3-L1 cells.Methods: We performed in-vitro experiments like MTT assay, Oil Red O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis in 3T3-L1 cells. In-vivo parameters like body weight gain, body composition, plasma adipokines, serum & liver lipid profiles, liver marker enzymes, western blot analysis and histopathological examination were conducted in rat model. In addition, molecular docking studies were also performed to understand interaction of BSTN1 with peroxisome proliferator-activated gamma receptor (PPAR-γ) and AMP-activated protein kinase (AMPK) which supported our experimental results.Results: BSTN1 at 20 μM significantly (p<0.001) inhibited cell differentiation and lipid accumulation of 3T3-L1 adipocytes. Mechanistic studies showed that mRNA expression of key adipogenic markers, PPAR-γ, fatty acid synthase (FAS) and sterol-regulatory element-binding protein-1 (SREBP1) were down-regulated while AMPK was up-regulated by BSTN1. Oral administration of BSTN1 (5 mg/kg. b.wt.) to HFD-induced obese rats substantially decreased body weight gain, fat mass, serum and liver lipid levels and promoted integrity of hepatic and adipose tissue architecture compared to HFD-control rats. In BSTN1 administered groups, decreased serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, decreased plasma leptin but increased adiponectin levels were noted. Western blot analysis of adipose and hepatic tissues collected from BSTN1 treated rats showed decreased expression level of PPAR-γ but increase in AMPK expression relative to the untreated group. In-silico studies showed strong binding interactions of BSTN1 against PPAR-γ and AMPK, the key molecules of adipogenesis and obesity.Conclusions: Taken together, the results suggest that BSTN1 could be promising molecule for the treatment of diet-induced obesity and non-alcoholic fatty liver disease (NAFLD).

scholarly journals Deletion of miRNA-22 Induces Cardiac Hypertrophy in Females but Attenuates Obesogenic Diet-Mediated Metabolic Disorders

2020 ◽  
Vol 54 (6) ◽  
pp. 1199-1217
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Metabolic Disorders ◽  
Body Weight Gain ◽  
Expression Profiles ◽  
Left Ventricular ◽  
Sequencing Analysis ◽  
Obesogenic Diet

Background/Aims: Obesity is a risk factor associated with cardiometabolic complications. Recently, we reported that miRNA-22 deletion attenuated high-fat diet-induced adiposity and prevented dyslipidemia without affecting cardiac hypertrophy in male mice. In this study, we examined the impact of miRNA-22 in obesogenic diet-induced cardiovascular and metabolic disorders in females. Methods: Wild type (WT) and miRNA-22 knockout (miRNA-22 KO) females were fed a control or an obesogenic diet. Body weight gain, adiposity, glucose tolerance, insulin tolerance, and plasma levels of total cholesterol and triglycerides were measured. Cardiac and white adipose tissue remodeling was assessed by histological analyses. Echocardiography was used to evaluate cardiac function and morphology. RNA-sequencing analysis was employed to characterize mRNA expression profiles in female hearts. Results: Loss of miRNA-22 attenuated body weight gain, adiposity, and prevented obesogenic diet-induced insulin resistance and dyslipidemia in females. WT obese females developed cardiac hypertrophy. Interestingly, miRNA-22 KO females displayed cardiac hypertrophy without left ventricular dysfunction and myocardial fibrosis. Both miRNA-22 deletion and obesogenic diet changed mRNA expression profiles in female hearts. Enrichment analysis revealed that genes associated with regulation of the force of heart contraction, protein folding and fatty acid oxidation were enriched in hearts of WT obese females. In addition, genes related to thyroid hormone responses, heart growth and PI3K signaling were enriched in hearts of miRNA-22 KO females. Interestingly, miRNA-22 KO obese females exhibited reduced mRNA levels of Yap1, Egfr and Tgfbr1 compared to their respective controls. Conclusion: This study reveals that miRNA-22 deletion induces cardiac hypertrophy in females without affecting myocardial function. In addition, our findings suggest miRNA-22 as a potential therapeutic target to treat obesity-related metabolic disorders in females.

scholarly journals The lysyl oxidase inhibitor  -aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats

2015 ◽  
Vol 8 (6) ◽  
pp. 543-551 ◽  
Author(s):  
M. Miana ◽  
M. Galan ◽  
E. Martinez-Martinez ◽  
S. Varona ◽  
R. Jurado-Lopez ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Metabolic Profile ◽  
Lysyl Oxidase ◽  
Body Weight Gain ◽  
Oxidase Inhibitor ◽  
Diet Induced Obesity

scholarly journals Gut microbiota in obesity and metabolic disorders

2010 ◽  
Vol 69 (3) ◽  
pp. 434-441 ◽  
Author(s):  
Yolanda Sanz ◽  
Arlette Santacruz ◽  
Paola Gauffin
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Dietary Intervention ◽  
Body Weight Gain ◽  
Human Subjects ◽  
Inflammatory Factors ◽  
Public Health Issue ◽  
Immune Functions

Obesity is a major public health issue as it is causally related to several chronic disorders, including type-2 diabetes, CVD and cancer. Novel research shows that the gut microbiota is involved in obesity and metabolic disorders, revealing that obese animal and human subjects have alterations in the composition of the gut microbiota compared to their lean counterparts. Moreover, transplantation of the microbiota of either obese or lean mice influences body weight in the germ-free recipient mice, suggesting that the gut ecosystem is a relevant target for weight management. Indigenous gut microbes may regulate body weight by influencing the host's metabolic, neuroendocrine and immune functions. The intestinal microbiota, as a whole, provides additional metabolic functions and regulates the host's gene expression, improving the ability to extract and store energy from the diet and contributing to body-weight gain. Imbalances in the gut microbiota and increases in plasma lipopolysaccharide may also act as inflammatory factors related to the development of atherosclerosis, insulin resistance and body-weight gain. In contrast, specific probiotics, prebiotics and related metabolites might exert beneficial effects on lipid and glucose metabolism, the production of satiety peptides and the inflammatory tone related to obesity and associated metabolic disorders. This knowledge is contributing to our understanding of how environmental factors influence obesity and associated diseases, providing new opportunities to design improved dietary intervention strategies to manage these disorders.

Abstract 295: Microsomal Prostaglandin E Synthase 1 Deficiency Attenuates Diet-Induced Obesity and Promotes the Formation of Brite Adipose Tissue

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Natalie J Moretz ◽  
Nicholas Hatch ◽  
Sarah Srodulski ◽  
Victoria L King
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Marked Reduction ◽  
Body Weight Gain ◽  
Prostaglandin E ◽  
Low Grade ◽  
Prostaglandin E Synthase ◽  
Diet Induced Obesity ◽  
Microsomal Prostaglandin E Synthase

Mice deficient in adipocyte specific phospholipases A2 have a marked reduction in prostaglandin E2 (PGE2) levels and are resistant to the development of diet-induced obesity. Clinical data suggest that obesity is a chronic low grade inflammatory disease, characterized by the influx of inflammatory cells into the adipose tissue. During a chronic inflammatory state, microsomal prostaglandin E synthase-1 (mPGES-1) is the primary source of PGE2. We have previously demonstrated that mice deficient in mPGES-1 (KO) have a marked reduction in body weight gain and adiposity compared to littermate controls (WT) fed a high fat (HF) diet with a concomitant reduction in urinary PGE2 concentrations and an increase in urinary PGI2 concentrations. The reduction in weight gain is not for accounted by alterations in food intake or locomotor activity. However, resting metabolic rate, measured by indirect calorimetry, was increased in KO mice compared to WT fed a HF diet. Moreover, body temperature was also increased in KO mice compared to WT mice (37.0 ± 0.2 vs 35.8 ± 0.2; P < 0.05) fed a HF diet. Taken together these data suggest that mPGES-1 deficiency increases energy expenditure in response to feeding a HF diet. Analysis of white adipose tissue (WAT) depots demonstrated an increase in number of smaller adipocytes per unit area in the KO mice compared to WT mice. The WAT from KO mice also had a marked decrease in triglyceride content, F4/80 staining and CD86 staining with a concomitant increase in CD206 staining suggesting an attenuation in macrophage recruitment into the WAT as well as an M2 phenotype. Additionally, COX-2 and UCP-1 and PPAR-γ expression were increased in WAT depots with a concomitant localization of multi-locular adipocytes in WAT depots, demonstrating the presence of brown adipocytes in WAT depots in KO mice fed a HF diet. These data suggest that the reduction in body weight gain in the KO mice may be due an increase in thermogenesis mediated by the formation of brite adipose tissue in WAT depots.

scholarly journals Melatonin Reduces Body Weight Gain in Sprague Dawley Rats with Diet-Induced Obesity

Endocrinology ◽  
2003 ◽  
Vol 144 (12) ◽  
pp. 5347-5352 ◽  
Author(s):  
Bénédicte Prunet-Marcassus ◽  
Mathieu Desbazeille ◽  
Arnaud Bros ◽  
Katie Louche ◽  
Philippe Delagrange ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats
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