Diet-dependent natriuretic peptide receptor C expression in adipose tissue is mediated by PPARγ via long-range distal enhancers

Shi, Fubiao; Simándi, Zoltán; Nagy, László; Collins, Sheila

doi:10.1016/j.jbc.2021.100941

Cited by 10 publications

(11 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Cross Talk Between Heart and Peripheral Metabolismmentioning

confidence: 99%

“…178 Natriuretic peptides are secreted from hypertrophied and failing hearts. Adipose tissues express natriuretic peptide receptors, 179 activation of which may lead to browning of adipose tissue and increased energy expenditure. 180 Thus, natriuretic peptide secretion from the failing heart could contribute to altered systemic metabolism and potentially cachexia in patients with HF.…”

Section: Lessons Learned From Genetic Models Of Altered Cardiac Metab...mentioning

confidence: 99%

See 1 more Smart Citation

Animal Models of Dysregulated Cardiac Metabolism

Bugger

Byrne

Abel

2022

Circulation Research

View full text Add to dashboard Cite

As a muscular pump that contracts incessantly throughout life, the heart must constantly generate cellular energy to support contractile function and fuel ionic pumps to maintain electrical homeostasis. Thus, mitochondrial metabolism of multiple metabolic substrates such as fatty acids, glucose, ketones, and lactate is essential to ensuring an uninterrupted supply of ATP. Multiple metabolic pathways converge to maintain myocardial energy homeostasis. The regulation of these cardiac metabolic pathways has been intensely studied for many decades. Rapid adaptation of these pathways is essential for mediating the myocardial adaptation to stress, and dysregulation of these pathways contributes to myocardial pathophysiology as occurs in heart failure and in metabolic disorders such as diabetes. The regulation of these pathways reflects the complex interactions of cell-specific regulatory pathways, neurohumoral signals, and changes in substrate availability in the circulation. Significant advances have been made in the ability to study metabolic regulation in the heart, and animal models have played a central role in contributing to this knowledge. This review will summarize metabolic pathways in the heart and describe their contribution to maintaining myocardial contractile function in health and disease. The review will summarize lessons learned from animal models with altered systemic metabolism and those in which specific metabolic regulatory pathways have been genetically altered within the heart. The relationship between intrinsic and extrinsic regulators of cardiac metabolism and the pathophysiology of heart failure and how these have been informed by animal models will be discussed.

show abstract

Section: Cross Talk Between Heart and Peripheral Metabolismmentioning

confidence: 99%

Section: Lessons Learned From Genetic Models Of Altered Cardiac Metab...mentioning

confidence: 99%

Animal Models of Dysregulated Cardiac Metabolism

Bugger

Byrne

Abel

2022

Circulation Research

View full text Add to dashboard Cite

show abstract

“…HIB-1B cells were seeded in 6-well plate at a density of 5 x 10 5 cells/well and reached 90% confluence when ready for transfection the following day. Cells were transfected with 2.5 μg/well shRNA knockdown (pLKO.1-puro) or SIK3 expression (Lenti-mSIK3-3xFlag-Puro) plasmids by PEI reagent as previously described [65]. Six-hours after transfection, cells were induced for differentiation in Growth Medium with 1 μM rosiglitazone.…”

Section: Shrna Knockdown and Sik3 Over-expressionmentioning

confidence: 99%

Salt-inducible kinase inhibition promotes the adipocyte thermogenic program and adipose tissue browning

Shi

Silva

Liu

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Norepinephrine stimulates the adipose tissue thermogenic program through a beta-adrenergic receptor (Beta AR) - cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) signaling cascade. Previous work from our lab showed that noncanonical activation of the mechanistic target of rapamycin complex 1 (mTORC1) by PKA is required for the beta AR-stimulation of adipose tissue browning. However, the downstream events triggered by mTORC1 activation that drive this thermogenic response are not well understood. In this study, we used a proteomic approach of Stable Isotope Labeling by/with Amino acids in Cell culture (SILAC) to characterize the global protein phosphorylation profile in brown adipocytes with beta-agonist isoproterenol stimulation and identified salt-inducible kinase 3 (SIK3) as a candidate mTORC1 substrate. SIK3 interacts with RAPTOR, the defining component of the mTORC1 complex, and is phosphorylated at Ser 884 in a mTORC1-dependent manner. Pharmacological SIK inhibition by a pan-SIK inhibitor (HG-9-91-01) in brown adipocytes increases basal Ucp1 gene expression and restores its expression upon either mTORC1 or PKA blockades. Short-hairpin RNA knockdown of Sik3 augments, while overexpression of SIK3 suppresses, Ucp1 gene expression in brown adipocytes. In addition, CRISPR gene-edited Sik3-/- brown adipocytes show enhanced Ucp1 gene expression at basal conditions and after Iso stimulation. Finally, a SIK inhibitor well-tolerated in vivo (YKL-05-099) can stimulate adipose tissue browning and thermogenic gene expression in mouse subcutaneous inguinal adipose tissue, supporting an essential role of SIK inhibition in regulating the adipose tissue browning program in vivo. Taken together, our data reveal that salt-inducible kinases function as a phosphorylation switch for beta-adrenergic activation to drive the adipose thermogenic program and suggest that maneuvers targeting SIKs could be beneficial for obesity and related metabolic disease.

show abstract

“…Adipose tissue lipolysis is also stimulated by natriuretic peptides (NPs), which play a key role in maintaining blood pressure and fluid volume. Under overnutrition conditions, PPARγ upregulates high-fat diet (HFD)-dependent NP receptor C (Nprc) expression in adipocytes through long-range distal transcriptional regulation, and thereby attenuates adipocyte NP signaling in obesity [42]. Mitochondrial activity plays an important role in the health and function of adipose tissue.…”

Section: Pparγmentioning

confidence: 99%

PPARs-Orchestrated Metabolic Homeostasis in the Adipose Tissue

Sun

Mao

Chen

et al. 2021

IJMS

View full text Add to dashboard Cite

It has been more than three decades since peroxisome proliferator-activated receptors (PPARs) were first discovered. Many investigations have revealed the central regulators of PPARs in lipid and glucose homeostasis in response to different nutrient conditions. PPARs have attracted much attention due to their ability to improve metabolic syndromes, and they have also been proposed as classical drug targets for the treatment of hyperlipidemia and type 2 diabetes (T2D) mellitus. In parallel, adipose tissue is known to play a unique role in the pathogenesis of insulin resistance and metabolic syndromes due to its ability to “safely” store lipids and secrete cytokines that regulate whole-body metabolism. Adipose tissue relies on a complex and subtle network of transcription factors to maintain its normal physiological function, by coordinating various molecular events, among which PPARs play distinctive and indispensable roles in adipocyte differentiation, lipid metabolism, adipokine secretion, and insulin sensitivity. In this review, we discuss the characteristics of PPARs with special emphasis on the roles of the different isotypes in adipocyte biology.

show abstract

Diet-dependent natriuretic peptide receptor C expression in adipose tissue is mediated by PPARγ via long-range distal enhancers

Cited by 10 publications

References 52 publications

Animal Models of Dysregulated Cardiac Metabolism

Animal Models of Dysregulated Cardiac Metabolism

Salt-inducible kinase inhibition promotes the adipocyte thermogenic program and adipose tissue browning

PPARs-Orchestrated Metabolic Homeostasis in the Adipose Tissue

Contact Info

Product

Resources

About