CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1253981 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33246012_1.fastq.gz | Fastqsanger.gz | |||
| SRR33246012_2.fastq.gz | Fastqsanger.gz | |||
| SRR33246013_1.fastq.gz | Fastqsanger.gz | |||
| SRR33246013_2.fastq.gz | Fastqsanger.gz | |||
| SRR33246014_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 92 |
Similar Datasets
Project description:CagriSema is a combination of amylin (cagrilintide) and glucagon-like peptide-1 (semaglutide) analogues being developed for weight management. We quantified CagriSema’s action on energy intake and expenditure in rats. CagriSema caused 12% weight loss and a 39% reduction in food intake. In contrast, pair-feeding caused less weight loss while weight-matching required a 51% decrease in food intake. Approximately 1/3 of CagriSema’s weight loss efficacy was from an energy expenditure effect, blunting of metabolic adaptation, which is likely a hallmark of successful treatment of obesity.
2025-04-23 | GSE295272 | GEO
Project description:The combination of decreasing food intake and increasing energy expenditure represents a powerful strategy for counteracting cardiometabolic diseases, such as obesity and type 2 diabetes1. Yet current approaches require conjugating multiple receptor agonists to achieve both effects2–4 and, thus far, no safe energy-expending option has reached the clinic. Here we show that activation of Neurokinin 2 Receptor (NK2R) is sufficient to suppress appetite centrally and increase energy expenditure peripherally. We focused on NK2R after discovering its genetic links to obesity and glucose control. However, therapeutically exploiting NK2R signalling has previously been unattainable because its endogenous ligand, Neurokinin A (NKA), is short-lived and lacks receptor specificity5,6. Therefore, we developed selective, long-acting NK2R agonists, with potential for once-weekly administration in humans. In mice, these agonists elicit weight loss by inducing energy expenditure and non-aversive appetite suppression that circumvents canonical leptin signalling. Additionally, a hyperinsulinemic-euglycemic clamp reveals that NK2R agonism acutely enhances insulin sensitization. In diabetic, obese nonhuman primates, NK2R activation significantly decreases body weight, blood glucose, triglycerides, and cholesterol, and ameliorates insulin resistance. These findings identify a single receptor target that leverages both energy-expending and appetite-suppressing programs to improve energy homeostasis and reverse cardiometabolic dysfunction across species.
2024-11-27 | GSE276735 | GEO
Project description:The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to optimize fuel mobilization and storage. Specifically, increased brain-melanocortin signaling or negative energy balance promotes lipid mobilization by increasing Sympathetic Nervous input to adipose tissue. In contrast, calorie-independent mechanisms favoring energy storage are less understood. Here we demonstrate that obesogenic signals, including reduction of brain-melanocortin signaling or high-fat feeding, actively promote fat mass gain independently of caloric intake via efferent nerve fibers conveyed by the common hepatic branch of the vagus nerve. These signals promote adipose tissue expansion by activating lipogenic program and adipocyte and endothelial cell proliferation independently of insulin action or the sympathetic tone to adipose tissue. These data reveal a novel physiological mechanism whereby the brain controls energy stores that may contribute to increased susceptibility to obesity.
2019-04-18 | GSE128383 | GEO
Project description:Dietary protein restriction has been shown to increase energy expenditure and to improve insulin sensitivity in mice, but it is unknown whether humans exhibit similar phenotype to a prolonged eucaloric protein-restricted diet that meet daily protein minimum requirements. We hypothesize that a protein-restricted diet would necessitate an increase in energy intake in order to maintain body weight in healthy, lean men. We designed an overall amino acid diluted diet meeting the requirement for daily protein intake and essential amino acids. Healthy, young, lean men adhered to a protein-restricted, high-carbohydrate diet (LPHC: protein 9E%, 70E% carbohydrate, and 21E% fat) or a protein-restricted, high-fat diet (LPHF: 9E% protein, 50E% fat, and 40E% carbohydrate) for 5 weeks, followed by another 5 weeks on a higher, standard protein diet (HPD: 18E% protein), reflecting their habitual diet. The diets were eucaloric, and energy provision was adjusted to maintain body weight throughout the interventions. In addition, wild type (WT), and FGF21 knockout mice were also fed LPHC, LPHF diets, or a standard higher diet (HPD) for a total of 10 weeks. Our results showed that prolonged eucaloric LPHC and LPHF diets necessitated a daily increase of 20-21% (2.5 MJ) in food intake to maintain body weight compared to pre-intervention in healthy, lean men. Additionally, fasting plasma FGF21 levels increased from 90±125 pg/ml and 78±34 pg/ml to 257±99 pg/ml and 160±52 pg/ml at the end of the LPHC and LPHF, respectively. Furthermore, proteomic analysis revealed adaptations in the respiratory chain in human adipose tissue after 5-week protein-restricted diets. This was found to be dependent on FGF21 in mice, indicating increased energy utilization through alternative UCP1-independent futile cycle pathways likely mediated by FGF21. Moreover, whole-body insulin sensitivity, measured by a hyperinsulinemic-euglycemic clamp, was increased by 16% after the LPHC intervention while maintained after the LPHF intervention, despite the high fat intake. These findings suggest that a protein-restricted diet could serve as a promising approach to prevent weight gain and comorbidities associated with obesity.
2025-04-22 | PXD047177 | Pride
Project description:Steap4, highly expressed in adipose tissue, is associated with metabolic homeostasis. Dysregulated adipose and mitochondrial metabolism contribute to obesity, highlighting the need to understand their interplay. Whether and how Steap4 influences mitochondrial function, adipocytes, and energy expenditure remains unclear. Adipocyte-specific Steap4-deficient mice exhibited increased fat mass and severe insulin resistance in our high-fat diet model. Mass spectrometry identified two classes of Steap4 interactomes: mitochondrial proteins and proteins involved in splicing. RNA-seq analysis of white adipose tissue demonstrated that Steap4 deficiency altered RNA splicing patterns with enriched mitochondrial functions. Indeed, Steap4 deficiency impaired respiratory chain complex activity, causing mitochondrial dysfunction in white adipose tissue. Consistently, brown adipocyte-specific Steap4 deficiency impaired mitochondrial function, increased brown fat whitening, reduced energy expenditure, and exacerbated insulin resistance in a high-fat model. Overall, our study highlights Steap4’s critical role in modulating adipocyte mitochondrial function, thereby controlling thermogenesis, energy expenditure, and adiposity.
2025-02-03 | GSE247291 | GEO
Project description:Late eating has been linked to obesity risk. It is not clear whether this is caused by changes in hunger and appetite, energy expenditure or both, nor what molecular pathways in adipose tissues are involved. We conducted a randomized crossover trial to determine the effects of late vs. early meal schedule on the above measures while rigorously controlling for nutrient intake, fasting duration, light exposure, physical activity and sleep opportunity. Late mealtimes doubled the odds of participants reporting hunger (p<0.0001), increased 24-h ghrelin:leptin ratio (p<0.0001) and decreased waketime energy expenditure (p=0.002). Adipose biopsy directional gene expression analyses showed alterations of several pathways attributed to late mealtimes: TGF-β signaling, lipid metabolism, p38 MAPK signaling, modulation of receptor tyrosine kinases, and autophagy, indicating decreased lipolysis/increased lipid synthesis, particularly for phospholipids and membrane-bound lipids. These findings may help develop evidence-based approaches for using appropriate meal timing to prevent and/or treat obesity.
2021-12-06 | GSE190166 | GEO
Project description:Obesity occurs when energy expenditure is outweighed by food intake. Tuberal hypothalamic nuclei, including the arcuate nucleus (ARC), ventromedial nucleus (VMH), and dorsomedial nucleus (DMH), regulate feeding amount as well as energy expenditure. Here we report that mice lacking circadian nuclear receptors REV-ERBa and b in the tuberal hypothalamus (HDKO) gain excessive weight on an obesogenic diet due both to decreased energy expenditure and increased food consumption during the light phase. Moreover, rebound food intake after fasting is markedly increased in HDKO mice. Integrative transcriptomic and cistromic analyses revealed that such disruption in feeding behavior is due to perturbed REV-ERB-dependent leptin signaling in the ARC. Indeed, in vivo leptin sensitivity is impaired in HDKO mice on an obesogenic diet in a circadian manner. Thus, REV-ERBs play a crucial role in hypothalamic regulation of food intake and circadian leptin sensitivity in diet-induced obesity.
2020-10-11 | GSE148641 | GEO
Project description:Obesity occurs when energy expenditure is outweighed by food intake. Tuberal hypothalamic nuclei, including the arcuate nucleus (ARC), ventromedial nucleus (VMH), and dorsomedial nucleus (DMH), regulate feeding amount as well as energy expenditure. Here we report that mice lacking circadian nuclear receptors REV-ERBa and b in the tuberal hypothalamus (HDKO) gain excessive weight on an obesogenic diet due both to decreased energy expenditure and increased food consumption during the light phase. Moreover, rebound food intake after fasting is markedly increased in HDKO mice. Integrative transcriptomic and cistromic analyses revealed that such disruption in feeding behavior is due to perturbed REV-ERB-dependent leptin signaling in the ARC. Indeed, in vivo leptin sensitivity is impaired in HDKO mice on an obesogenic diet in a circadian manner. Thus, REV-ERBs play a crucial role in hypothalamic regulation of food intake and circadian leptin sensitivity in diet-induced obesity.
2020-10-11 | GSE148599 | GEO
Project description:Lipoprotein Lipase Overexpression in Skeletal Muscle Attenuates Weight Regain by Potentiating Energy Expenditure
| PRJNA647913 | ENA