Cardioprotective Effects of Sirtuin-1 and Its Downstream Effectors

  title={Cardioprotective Effects of Sirtuin-1 and Its Downstream Effectors},
  author={Milton Packer},
  journal={Circulation: Heart Failure},
  • M. Packer
  • Published 1 September 2020
  • Biology
  • Circulation: Heart Failure
The cardioprotective effects of SGLT2 (sodium-glucose cotransporter 2) inhibitors may be related to their ability to induce a fasting-like paradigm, which triggers the activation of nutrient deprivation pathways to promote cellular homeostasis. The most distinctive metabolic manifestations of this fasting mimicry are enhanced gluconeogenesis and ketogenesis, which are not seen with other antihyperglycemic drugs. The principal molecular stimulus to gluconeogenesis and ketogenesis is activation… 

Figures from this paper

SGLT2 inhibitors as calorie restriction-mimetics: insights on longevity pathways and age-related diseases.

Modulation of multiple longevity pathways by SGLT2 inhibitors have been shown to alleviate metabolic diseases, attenuate vascular inflammation and arterial stiffness, improve mitochondrial function and reduce oxidative stress-induced tissue damage.

Sodium–Glucose Cotransporter 2 Inhibitors Work as a “Regulator” of Autophagic Activity in Overnutrition Diseases

A small number of studies suggest that S GLT2 inhibitors not only activate but also suppress the autophagy flux depending on the situation, indicating that SGLT2 inhibitor can “regulate” autophagic activity and help achieve the appropriate autophile flux in each organ.

Monoterpenes as Sirtuin-1 Activators: Therapeutic Potential in Aging and Related Diseases

Current information on the evidence that supports the role of non-polyphenolic monoterpenoids as SIRT1 activators and their potential both as tools for research and as pharmaceuticals for therapeutic application in age-related diseases are discussed.

Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

The interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes—are attempted to discuss.

Characterization of the SGLT2 Interaction Network and Its Regulation by SGLT2 Inhibitors: A Bioinformatic Analysis

This study provides comprehensive and ranked information about the S GLT2 interaction network in the context of tissue expression and can help to predict the clinical effects of the SGLT2i.

Protective Effects of Curcumin in Cardiovascular Diseases—Impact on Oxidative Stress and Mitochondria

Curcumin as a nutraceutical could hold promise in the prevention of CVDs, but more standardized clinical trials are required to fully unravel its potential.



SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms.

It is demonstrated that SGLT2 inhibition triggers a fasting-like transcriptional and metabolic paradigm but requires FGF21 for reduction in adiposity, and that CANA induces transcriptional reprogramming to activate catabolic pathways.

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

It is demonstrated that SIRT1 and its activator, RSV, have clear anti-hyperuricemia functions in this mouse model and one possible mechanism is the activation of ABCG2 in the ileum through the PGC-1α/PPARγ pathway.

Sirt1 acts in association with PPARα to protect the heart from hypertrophy, metabolic dysregulation, and inflammation.

Findings reveal a major involvement of the Sirt1-PPARα interaction in the protective role of Sirt2 against cardiac hypertrophy and in vivo isoproterenol-induced cardiachypertrophy, metabolic dysregulation, and inflammation in vivo.

Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice.

It is suggested that FF could prevent Type 1 diabetes-induced pathological and functional abnormalities of the heart by increasing FGF21 that may up-regulate Sirt1-mediated autophagy.

Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway

LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway and could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR.

Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1

It is shown that the Sir2 homologue, SIRT1 controls the gluconeogenic/glycolytic pathways in liver in response to fasting signals through the transcriptional coactivator PGC-1α, and this findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan.

Multiple Levels of PGC-1α Dysregulation in Heart Failure

Recent studies revealing how PGC-1α is regulated by a multitude of mechanisms, operating at different regulatory levels, which include epigenetic regulation, the expression of variants, post-transcriptional inhibition, and post- translational modifications are summarized.