GDF15 reduces NAFLD through mechanisms that are independent of the suppression of food intake
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE229708 | GEO | 2023/04/14
REPOSITORIES: GEO
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Project description:The effects of recombinant human GDF15 on Sympathetic Nervous System (SNS) signalling in skeletal muscle during the caloric restriction in mice.
2023-04-14 | GSE229794 | GEO
Project description:Cancer cachexia is a disorder characterized by both involuntary weight loss and impaired physical performance. Decline in physical performance of patients with cachexia is associated with poor quality of life, and currently there are no effective pharmacological interventions that restore physical performance. Here we examined the effect of GDF15 neutralization in a mouse model of cancer-induced cachexia (TOV21G) that manifested weight loss and muscle function impairments. With comprehensive assessments, our results demonstrated that cachectic mice treated with the anti-GDF15 antibody mAB2 exhibited body weight gain with near-complete restoration of muscle mass and markedly improved muscle function and physical performance. Mechanistically, the improvements induced by GDF15 neutralization were primarily attributed to increased caloric intake, while altered gene expressions in cachectic muscles were restored in both caloric intake-dependent and -independent manners. The findings implicate the potential of GDF15 neutralization as an effective therapy to enhance physical performance of patients with cachexia.
2023-01-11 | GSE214603 | GEO
Project description:Rats (n=24) were fed ad libitum diets containing either ground endophyte-free (E-) seed or endophyte–infected (E+) seed for five days at thermoneutrality (21°C) or heat stress (32 C) for 21 days. Rats with intraperitonial transmitters were used with core temperature (Tc) and general activity measured every 5 minutes during the study. At treatment end, the liver was removed, weighed and frozen in liquid nitrogen. RNA was extracted from liver samples, converted to cDNA, and hybridized with the printed oligonucleotide slides. Treatments consisted of four treatment groups, E-TN, E+TN, E-HS, E+HS. E-TN IS control at thermoneutral for 26 days , E+TN toxin fed group at thermoneutral for 26 days; E-HS control at thermoneutral for 5 days and heat treatment for 21 days, E+HS is toxin fed group at thermoneutral for 5 days and heat stress for 21 days. Rats (n=24) were divided into two groups and fed with either E- or E+ diet for 5 days under TN conditions. At the end of TN period, each group was further subdivided into two groups each. Treatments consisted of four treatment groups, E-TN, E+TN, E-HS, E+HS. E-TN IS control at thermoneutral for 26 days , E+TN toxin fed group at thermoneutral for 26 days; E-HS control at thermoneutral for 5 days and heat treatment for 21 days, E+HS is toxin fed group at thermoneutral for 5 days and heat stress for 21 days.
2007-08-14 | E-GEOD-8754 | biostudies-arrayexpress
Project description:Rats (n=24) were fed ad libitum diets containing either ground endophyte-free (E-) seed or endophyte–infected (E+) seed for five days at thermoneutrality (21°C) or heat stress (32 C) for 21 days. Rats with intraperitonial transmitters were used with core temperature (Tc) and general activity measured every 5 minutes during the study. At treatment end, the liver was removed, weighed and frozen in liquid nitrogen. RNA was extracted from liver samples, converted to cDNA, and hybridized with the printed oligonucleotide slides. Treatments consisted of four treatment groups, E-TN, E+TN, E-HS, E+HS. E-TN IS control at thermoneutral for 26 days , E+TN toxin fed group at thermoneutral for 26 days; E-HS control at thermoneutral for 5 days and heat treatment for 21 days, E+HS is toxin fed group at thermoneutral for 5 days and heat stress for 21 days. Keywords: Stress response
2007-08-14 | GSE8754 | GEO
Project description:Growth Differentiation Factor 15 (GDF15) is a divergent member of the TGF-β superfamily, and its expression increases under various stress conditions, including inflammation, hyperoxia, and senescence. GDF15 expression is increased in neonatal murine BPD models, and GDF15 loss exacerbates oxidative stress and decreases viability in vitro in pulmonary epithelial and endothelial cells. Our overall hypothesis is that the loss of GDF15 will exacerbate hyperoxic lung injury in the neonatal lung in vivo. We exposed neonatal Gdf15-/- mice and wild-type (WT) controls on a similar background to room air or hyperoxia (95% O2) for 5 days after birth. The mice were euthanized on PND 21. Gdf15 -/- mice had higher mortality and lower body weight than WT mice after exposure to hyperoxia. Upon exposure to hyperoxia, female mice had higher alveolar simplification in the Gdf15-/- group than the female WT group. Gdf15-/- and WT mice showed no difference in the degree of the arrest in angiogenesis upon exposure to hyperoxia. Gdf15-/- mice showed lower macrophage count in the lungs compared to WT mice. Our results suggest that Gdf15 deficiency decreases the tolerance to hyperoxic lung injury with evidence of sex-specific differences.
2023-07-20 | GSE211744 | GEO
Project description:Mice have their lowest (basal) metabolic rate when housed at thermoneutrality, which starts above 29 degrees C. Although they eat less, and thus reduce their energy intake, their energy balance remains positive leading to an increased adiposity, especially when fed a high fat diet. However, almost all metabolic mouse studies are performed at standard room temperatures ranging between 20 and 22 degrees C. Previously, we showed that housing mice at thermoneutrality lead to massive increased adiposity, while metabolic dysfunction of white adipose tissue (WAT) was absent. Here, we studied whether an increased metabolic flux through WAT induces cellular stress and underlies tissue dysfunction leading to tissue inflammation. C57BL/6JOlaHsd wildtype male mice, aged 9 weeks, were fed purified low fat diet (BIOCLAIMS, Hoevenaars et al., Genes and Nutrition 2012) for 3 weeks to acclimatize, followed by 12 weeks a BIOCLAIMS high-fat diet (HFD), all at thermoneutrality (29 degrees C). Subsequently, mice were divided into different treatment groups: i) control group, which remained at thermoneutrality for 5 days, ii) 5 days normal housing temperature (22 C degrees) while housed continously in an indirect calorimetry system. At the end of the study, after 2 hours food removal at the start of the light phase, mice were killed immediately by decapitation after taking them out of the indirect calorimetry system. After sacrification, epididymal WAT was immediately dissected and snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 8x60K microarrays.
2017-04-06 | GSE53804 | GEO
Project description:Anorexia and other side effects of chemotherapy significantly limit the clinical applications of these chemotherapeutic agents, with underlying mechanisms still unclear. A growing body of research reveals that elevated levels of circulating GDF15 after chemotherapy are essential in initiating anorexia and other side effects by activating GFRAL+ neurons in the brainstem. However, the full array of context-dependent transcriptional regulators controlling Gdf15 expression remains to be defined. This study reports that chemotherapy drugs acutely stimulate liver GDF15 production via selective activation of the hepatic stress sensor IRE1α, thereby controlling circulating GDF15 levels. Genetic ablation of hepatic IRE1α reduces circulating GDF15 and alleviates anorexia and body weight loss following chemotherapy drug treatments in tumor-bearing mice. Mechanistically, chemotherapy drugs activate hepatic IRE1α RNase activity to produce the active form of the transcription factor XBP1 to promotes the expression of Gdf15 gene in hepatocytes. Moreover, treatment with pharmacological IRE1α RNase inhibitor effectively suppresses liver Gdf15 expression and circulating GDF15 levels, resulting in improvements in chemotherapy-induced anorexia and body weight loss. Our results reveal a stress-responsive mechanism that mediates communication between the liver and brain. This mechanism can be targeted pharmacologically to alleviate anorexic side effects that accompany chemotherapy-induced body weight loss.
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Project description:Spatial transcriptomics of brown adipose tissue from thermoneutrality (TN) and from mouse that had undergone transient acute cold exposure 4 days previously (1cyc)
2023-09-11 | GSE218710 | GEO
Project description:Caloric restriction is considered to be anti-inflammatory. In this study we examined the effect of fasting on peripheral leukocyte populations. We found that short-term fasting affects metabolic and pro-inflammatory activity of monocytes and decreases numbers of circulating monocytes. For this study, we sorted hepatocytes from fed and fasted mice, monocytes from bone marrow from fed and fasted mice, and monocytes from bone marrow from wildtype and Ccr2-deficient mice.
2019-02-22 | GSE126899 | GEO
Project description:The TGFβ cytokine family member, GDF15, reduces food intake and body weight and represents a potential treatment for obesity. Because the brain stem-restricted expression pattern of its receptor, GDNF Family Receptor α–like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake, we generated GfralCre and conditional GfralCreERT mice to visualize and manipulate GFRAL neurons. We found infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons. TRAP-Seq analysis of GFRAL neurons revealed their expression of a wide range of neurotransmitters and neuropeptides. Artificially activating GfralCre-expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), where they target CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated, pathophysiologic signals to suppress nutrient uptake and absorption.
2021-01-01 | GSE160257 | GEO