Hepatic GCGR is required for the superior weight loss effects of a structurally related analogue of the dual GCGR/GLP1R agonist survodutide DOI Creative Commons

Fen Long,

Manuel Klug,

Tenagne D. Challa

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Abstract The dual glucagon/glucagon-like peptide 1 receptor (GCGR/GLP1R) agonists have superior efficacy in promoting weight loss and metabolic improvements obesity dysfunction-associated steatohepatitis (MASH) than current available mono-agonists. However, the mechanisms underlying these benefits are not fully understood. While effects on appetite regulation glucose control through GLP1R agonism well established, role of GCGR changes is less defined. Using a GCGR/GLP1R agonist BI 456908 selective semaglutide, we could show that achieved by engaging hepatic without adversely affecting control. Furthermore, demonstrate critical for facilitating plasma liver lipid clearance stimulated agonist. Overall, findings highlight crucial contributions to combined GCGR/GL1R activation.

Language: Английский

Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes DOI Creative Commons
Tongtong Wang, Anand K. Sharma,

Chunyan Wu

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(9), P. 2130 - 2145.e7

Published: July 30, 2024

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 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 deconvolute heterogeneity of subcutaneous adipose in mice and humans, we identify at least 2 distinct subpopulations beige adipocytes: FC-adipocytes UCP1-beige adipocytes. Importantly, demonstrate FC-adipocyte subpopulation is highly metabolically active utilizes FCs energy, thus contributing thermogenesis independent Ucp1. Furthermore, are important drivers systemic homeostasis linked glucose metabolism obesity resistance humans. Taken together, our findings a noncanonical thermogenic adipocyte subpopulation, which could be an regulator mammals.

Language: Английский

Citations

9
Research article for 1st revision to the Chemico-Biological InteractionModulatory roles of capsaicin on thermogenesis in C2C12 myoblasts and the skeletal muscle of mice DOI

Alfin Mohammad Abdillah,

Jae Young Lee,

Young Rok Lee

et al.

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111380 - 111380

Published: Jan. 1, 2025

Language: Английский

Citations

1
The brain–body energy conservation model of aging DOI
Evan D. Shaulson, Alan A. Cohen, Martin Picard

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(10), P. 1354 - 1371

Published: Oct. 8, 2024

Language: Английский

Citations

7
An inter-organelle contact between endosomal GLP-1R, ER VAP-B, and the mitochondrial AKAP SPHKAP triggers PKA-dependent MIC19 phosphorylation and β-cell mitochondrial remodelling DOI
Gregory L. Austin, Liliane El Eid, Affiong I Oqua

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Abstract Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RAs) ameliorate mitochondrial health by increasing its turnover and improving quality control. While the GLP-1R is well known to stimulate cAMP production leading activation of Protein Kinase A (PKA) Exchange Activated cyclic AMP 2 (Epac2) signalling, there a lack understanding molecular mechanisms linking GLP-1RA-induced signalling with remodelling improved function. Here we present dataset that demonstrates that, following GLP-1RA stimulation in pancreatic β-cells, interacts endoplasmic reticulum (ER) membrane contact site (MCS) organising factor VAP-B from an endocytic location engage SPHKAP, A-kinase anchoring protein (AKAP) associated type diabetes (T2D) adiposity genome-wide association studies (GWAS), trigger pool mitochondrially localised PKA phosphorylates cristae organizing system (MICOS) complex component MIC19, enabling optimal β-cell

Language: Английский

Citations

4
Brown fat ATP-citrate lyase links carbohydrate availability to thermogenesis and guards against metabolic stress DOI
Ekaterina Korobkina,

Camila Martínez Calejman,

John D. Haley

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(11), P. 2187 - 2202

Published: Oct. 14, 2024

Language: Английский

Citations

4
Emerging debates and resolutions in brown adipose tissue research DOI
Aaron M. Cypess, Barbara Cannon, Jan Nedergaard

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

4
Dynamic Changes in Lipid Composition Reveal the Mechanism of Arachidonic Acid Accumulation in Mortierella alpina DOI

Yulong Zhao,

Lulu Chang, Bo Yang

et al.

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106019 - 106019

Published: Jan. 1, 2025

Language: Английский

Citations

0
Controlled burn: interconnections between energy-spilling pathways and metabolic signaling in bacteria DOI Creative Commons
Nicolaus A. Jakowec, Steven E. Finkel

Journal of Bacteriology, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

ABSTRACT Bacterial energy-spilling pathways—such as overflow metabolism and futile cycles—have been considered inefficient forms of that result from poor regulatory control or function mechanisms to cope with excess energy. However, mounting evidence places these seemingly wasteful reactions at the fulcrum between metabolic signaling stress adaptation in bacteria. Specifically, pathways may mediate reprogramming observed when cells encounter growth-limiting constraints (i.e., nutrient limitation). Recent insights spotlight microbial an intricate network coordinates physiological programming energy conditions. Such intracellular cross stalk is pivotal survival competitive, fluctuating environments bacteria frequently nature. In light this paradigm signaling, are increasingly recognized strategies enable rewiring response stress. Overflow cycles generate secondary metabolites properties, alter flux rate acquisition, stimulate nodes trigger specific programs environmental challenges. Furthermore, observation such expensive under laboratory conditions purported be “energy limiting” fact suggest sufficiency, compelling us rethink how we model limitation starvation for

Language: Английский

Citations

0
Quantification of nutrient fluxes during acute exercise in mice DOI
Jessie Axsom, Tara TeSlaa, Won Dong Lee

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

3
Ucp1 Ablation Improves Skeletal Muscle Glycolytic Function in Aging Mice DOI Creative Commons

Jin Qiu,

Yuhan Guo, Xiaozhen Guo

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 12(2)

Published: Nov. 21, 2024

Abstract Muscular atrophy is among the systematic decline in organ functions aging, while defective thermogenic fat functionality precedes these anomalies. The potential crosstalk between adipose tissue and muscle during aging poorly understood. In this study, it showed that UCP1 knockout (KO) mice characterized deteriorated brown (BAT) function yet their glucose homeostasis sustained energy expenditure increased, possibly compensated by improved inguinal (iWAT) compared to age‐matched WT mice. To understand crosstalk, RNA‐seq metabolomic analysis were performed on revealed creatine levels are increased both iWAT of KO Interestingly, molecular metabolite tracing biosynthesis uptake mice, suggesting transportation from muscle. Importantly, analog β‐GPA abolished differences inhibitor α‐CD glycolytic metabolism Overall, results suggested skeletal compensate for declined BAT via sustain metabolic homeostasis.

Language: Английский

Citations

3