Revati Sumukh Dewal


Last Name

Dewal

First Name

Revati Sumukh

ORCID

0000-0002-7765-8703

Organisational unit

Filters

2023 - 20255
Reset filters

Search Results

Publications 1 - 5 of 5
  • Adipocyte-specific deletion of gp130 prevents ketogenic diet-induced hepatic steatosis
    Item type: Journal Article
    Senkalfa, Berkay; Gloor, Melanie; Podlaszewski, Ronja; et al. (2025)
    Hepatology Communications
    Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of obesity and type 2 diabetes, can progress to metabolic dysfunction-associated steatohepatitis and fibrosis. MASLD is characterized by elevated hepatic lipid accumulation (steatosis) and insulin resistance. The ketogenic diet (KD), a high-fat, low-carbohydrate diet, induces hepatic insulin resistance and steatosis in animal models through unknown mechanisms. Methods and Results: Herein, we investigated the mechanisms behind KD-induced metabolic dysfunction-associated steatohepatitis and fibrosis at thermoneutrality, identifying upregulated inflammatory and lipogenic pathways, including Il-6, Tnf, Mapk13, Lpl, and Pparg. Given the substantial increase in IL-6 during MASLD progression, we investigated IL-6-gp130 signaling using liver- and adipocyte-specific knockout mice. Liver-specific gp130 deletion failed to prevent KD-induced hepatic steatosis and glucose intolerance. In contrast, adipocyte-specific gp130 deletion significantly reduced KD-induced hepatic steatosis by suppressing lipolysis in white adipose tissue and reducing p-JNK and p-p38 signaling in the liver. In agreement, adipocyte-specific deletion of gp130 protected mice from KD-induced hepatic steatosis in response to recombinant IL-6 treatment. Conclusions: Our studies demonstrate the importance of adipose tissue-liver crosstalk in mediating MASLD progression and identify adipocyte IL-6-gp130 as a potential therapeutic target.
  • Master of disguise: deconvoluting adipose tissue heterogeneity and its impact on metabolic health
    Item type: Review Article
    Dewal, Revati Sumukh; Wolfrum, Christian (2023)
    Current Opinion in Genetics & Development
    Adipose tissue in its different forms: white, brown, and beige, while essential in day-to-day bodily functions, leads to several disorders when present in overabundance, including obesity and type-2 diabetes. Adipose tissue function/dysfunction is largely mediated by the diversity of its cell composition, within adipocytes and cells in its stromal fraction. Owing to its heterogeneous nature, recent studies have focused on intercalating the effects of cellular diversity with adipose tissue function, particularly by employing sequencing technologies. In this review, we highlight the recent advances in utilizing single-cell and single-nuclei RNA sequencing technologies to discover novel adipose tissue cell types or subtypes, and to determine their role in mediating tissue, as well as whole-body metabolism and function.
  • Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes
    Item type: Journal Article
    Wang, Tongtong; Sharma, Anand Kumar; Wu, Chunyan; et al. (2024)
    Cell Metabolism
    Adipose tissue can recruit catabolic adipocytes that utilize chemical energy to dissipate heat. This process occurs either by uncoupled respiration through uncoupling protein 1 (UCP1) or by utilizing ATP-dependent futile cycles (FCs). However, it remains unclear how these pathways coexist since both processes rely on the mitochondrial membrane potential. Utilizing single-nucleus RNA sequencing to deconvolute the heterogeneity of subcutaneous adipose tissue in mice and humans, we identify at least 2 distinct subpopulations of beige adipocytes: FC-adipocytes and UCP1-beige adipocytes. Importantly, we demonstrate that the FCadipocyte subpopulation is highly metabolically active and utilizes FCs to dissipate energy, thus contributing to thermogenesis independent of Ucp1. Furthermore, FC-adipocytes are important drivers of systemic energy homeostasis and linked to glucose metabolism and obesity resistance in humans. Taken together, our findings identify a noncanonical thermogenic adipocyte subpopulation, which could be an important regulator of energy homeostasis in mammals.
  • Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis
    Item type: Journal Article
    Dewal, Revati Sumukh; Yang, Felix T.; Baer, Lisa A.; et al. (2024)
    iScience
    Obesity and its co-morbidities including type 2 diabetes are increasing at epidemic rates in the U.S. and worldwide. Brown adipose tissue (BAT) is a potential therapeutic to combat obesity and type 2 diabetes. Increasing BAT mass by transplantation improves metabolic health in rodents, but its clinical translation remains a challenge. Here, we investigated if transplantation of 2–4 million differentiated brown pre-adipocytes from mouse BAT stromal fraction (SVF) or human pluripotent stem cells (hPSCs) could improve metabolic health. Transplantation of differentiated brown pre-adipocytes, termed “committed pre-adipocytes” from BAT SVF from mice or derived from hPSCs improves glucose homeostasis and insulin sensitivity in recipient mice under conditions of diet-induced obesity, and this improvement is mediated through the collaborative actions of the liver transcriptome, tissue AKT signaling, and FGF21. These data demonstrate that transplantation of a small number of brown adipocytes has significant long-term translational and therapeutic potential to improve glucose metabolism.
  • Antibiotic-induced gut microbiota depletion enhances glucose tolerance linked to GLP-1 signaling
    Item type: Journal Article
    Kellenberger, Alexandra; Dewal, Revati Sumukh; de Wouters d’Oplinter, Alice; et al. (2025)
    Frontiers in Endocrinology
    Introduction: Depletion of the gut microbiota is known to improve glucose metabolism and modify thermogenic capacity in mice. However, the underlying mechanisms remain unclear. In this study, we aimed to determine whether the browning effect observed after antibiotic treatment contributes to metabolic modifications and to investigate the potential central role of GLP-1 in enhancing glucose metabolism. Methods: Using an inducible Ucp1DTR mouse model to transiently ablate UCP1+ cells, we assessed glucose tolerance, cold sensitivity, and circulating GLP-1 levels following gut microbiota depletion. We additionally examined GLP-1 levels in germ-free mice. Glucose tolerance was compared to GLP1R KO mice following gut microbiota depletion. Bile acid profiling in wild-type mice treated with antibiotics identified regulated bile acids, which were subsequently tested in an in vitro STC-1 cell assay and in vivo in Cyp2c70 mice to identify potential basal GLP-1 secretion inhibitors. Results: We demonstrate that gut microbiota depletion improved glucose tolerance independent of UCP1+ cell presence and increased cold sensitivity. Antibiotic treatment increased circulating active GLP-1 levels within one day, and this increase was also observed in germ-free mice, supporting the suggestion that GLP-1 elevation is driven by gut microbiota depletion. The improvement in glucose tolerance was lost in GLP1R KO mice upon oral glucose ingestion. Bile acid profiling and subsequent validation led to the identification of two potential basal GLP-1 secretion inhibitors. Discussion: Our findings suggest that the metabolic improvements following gut microbiota depletion are primarily driven by GLP-1 signaling, rather than UCP1⁺ cell activation. These results highlight the complex interplay between the gut microbiome and metabolic health, offering insights into potential therapeutic targets for improving glucose metabolism through modulation of basal GLP-1 signaling.
Publications 1 - 5 of 5