bims-hafaim 2023-12-24 papers

Issue of 2023–12–24
five papers selected by
Kyle McCommis, Saint Louis University

Front Cardiovasc Med. 2023 ;10 1291450

The changes of cardiac energy metabolism with sodium-glucose transporter 2 inhibitor therapy.

Sha Su, Xiang Ji, Tong Li, Yu Teng, Baofu Wang, Xiaowan Han, Mingjing Zhao.

Background/aims: To investigate the specific effects of s odium-glucose transporter 2 inhibitor (SGLT2i) on cardiac energy metabolism.
Methods: A systematic literature search was conducted in eight databases. The retrieved studies were screened according to the inclusion and exclusion criteria, and relevant information was extracted according to the purpose of the study. Two researchers independently screened the studies, extracted information, and assessed article quality.
Results: The results of the 34 included studies (including 10 clinical and 24 animal studies) showed that SGLT2i inhibited cardiac glucose uptake and glycolysis, but promoted fatty acid (FA) metabolism in most disease states. SGLT2i upregulated ketone metabolism, improved the structure and functions of myocardial mitochondria, alleviated oxidative stress of cardiomyocytes in all literatures. SGLT2i increased cardiac glucose oxidation in diabetes mellitus (DM) and cardiac FA metabolism in heart failure (HF). However, the regulatory effects of SGLT2i on cardiac FA metabolism in DM and cardiac glucose oxidation in HF varied with disease types, stages, and intervention duration of SGLT2i.
Conclusion: SGLT2i improved the efficiency of cardiac energy production by regulating FA, glucose and ketone metabolism, improving mitochondria structure and functions, and decreasing oxidative stress of cardiomyocytes under pathological conditions. Thus, SGLT2i is deemed to exert a benign regulatory effect on cardiac metabolic disorders in various diseases.
Systematic review registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42023484295).

Keywords: energy metabolism; fatty acid; glucose; heart; ketone body; sodium-glucose transporter 2 inhibitor

DOI: https://doi.org/10.3389/fcvm.2023.1291450

Front Pharmacol. 2023 ;14 1341004

Editorial: Molecular mechanism and pharmacology of metabolism and cardiac remodeling.

Mengya Chen, Saiyang Xie, Wei Deng.

Keywords: cardiac remodeling; heart failure; immunometabolism; metabolism; molecular mechanism

DOI: https://doi.org/10.3389/fphar.2023.1341004

Endocrinol Diabetes Metab Case Rep. 2023 Oct 01. pii: 23-0086. [Epub ahead of print]2023(4):

A low-carbohydrate diet in place of SGLT2i therapy in a patient with diabetic cardiomyopathy.

Sabine Kleissl-Muir, Bodil Rasmussen, Alice Owen, Caryn Zinn, Andrea Driscoll.

Summary: In patients with diabetes mellitus, the toxic milieu caused by abnormal glucose and free fatty acid handling can lead to heart failure (HF). Referred to as diabetic cardiomyopathy (DMCM), this syndrome often exists in the absence of conventional risk factors for HF such as history of myocardial infarction or hypertension. Low-carbohydrate diets (LCDs) have recently been endorsed as an efficacious therapeutic dietary approach to prevent and reverse cardiometabolic disease including type 2 diabetes mellitus (T2DM). LCDs improve systemic insulin resistance (IR), reverses cardiac remodelling in a rodent model and downregulates the expression of sodium-glucose co-transporter 2 (SGLT2) receptors in the kidney. It is therefore conceivable that a lifestyle approach such as adopting an LCD can be offered to patients with DMCM. The reported case is that of a 45-year-old man with a 15-year history of non-ischaemic cardiomyopathy, T2DM and obesity. The patient volunteered to engage in a 16-week low-carbohydrate dietary intervention trial and then self-selected to remain on this diet for 1 year. The whole-food LCD was based on simple 'traffic light' style food lists and not designed to restrict calories, protein, fat or salt. After 1 year, the patient had lost 39 kg and his cardiometabolic markers had significantly improved. LCDs present a potentially beneficial approach for patients with DMCM and could be considered as a lifestyle intervention before SGLT2i therapy is commenced.
Learning points: Diabetic cardiomyopathy (DMCM) is a syndrome precipitated mainly by the detrimental effects of glucose metabolism disorders such as insulin resistance and diabetes. Low-carbohydrate diets (LCD) mimic many effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i). LCDs are a dietary pattern which can have significant and beneficial effects on metabolic and anthropometric markers in patients with DMCM. LCDs and SGLT2i therapy could be combined and may achieve better clinical outcomes for patients with DMCM. Combination therapy may be carried out under close supervision as the real risk for diabetic ketoacidosis remains.

DOI: https://doi.org/10.1530/EDM-23-0086

Cell Rep Med. 2023 Dec 19. pii: S2666-3791(23)00551-7. [Epub ahead of print]4(12): 101334

Dapagliflozin protects against chronic heart failure in mice by inhibiting macrophage-mediated inflammation, independent of SGLT2.

Qingqing Wu, Qi Yao, Tongtong Hu, Jiabin Yu, Kebing Jiang, Ying Wan, Qizhu Tang.

The specific mechanism of sodium-glucose cotransporter 2 (SGLT2) inhibitor in heart failure (HF) needs to be elucidated. In this study, we use SGLT2-global-knockout (KO) mice to assess the mechanism of SGLT2 inhibitor on HF. Dapagliflozin ameliorates both myocardial infarction (MI)- and transverse aortic constriction (TAC)-induced HF. Global SGLT2 deficiency does not exert protection against adverse remodeling in both MI- and TAC-induced HF models. Dapagliflozin blurs MI- and TAC-induced HF phenotypes in SGLT2-KO mice. Dapagliflozin causes major changes in cardiac fibrosis and inflammation. Based on single-cell RNA sequencing, dapagliflozin causes significant differences in the gene expression profile of macrophages and fibroblasts. Moreover, dapagliflozin directly inhibits macrophage inflammation, thereby suppressing cardiac fibroblasts activation. The cardio-protection of dapagliflozin is blurred in mice treated with a C-C chemokine receptor type 2 antagonist. Taken together, the protective effects of dapagliflozin against HF are independent of SGLT2, and macrophage inhibition is the main target of dapagliflozin against HF.

Keywords: dapagliflozin; fibrosis; inflammation; macrophages; single-cell transcriptomics

DOI: https://doi.org/10.1016/j.xcrm.2023.101334

Biomedicines. 2023 Dec 01. pii: 3197. [Epub ahead of print]11(12):

Association between Serum Free Fatty Acids and Clinical and Laboratory Parameters in Acute Heart Failure Patients.

Iva Klobučar, Helga Hinteregger, Margarete Lechleitner, Matias Trbušić, Gudrun Pregartner, Andrea Berghold, Wolfgang Sattler, Saša Frank, Vesna Degoricija.

Very little is known about the association between individual serum free fatty acids (FFAs) and clinical and laboratory parameters (indicators of heart failure severity) in acute heart failure (AHF) patients. Here, the baseline serum levels of FFAs, 16:0 (palmitic acid), 16:1 (palmitoleic acid), 18:0 (stearic acid), 18:1 (oleic acid), 18:2 (linoleic acid), 18:3 (alpha-linolenic acid or gamma-linolenic acid), 20:4 (arachidonic acid), 20:5 (eicosapentaenoic acid), and 22:6 (docosahexaenoic acid), were determined in 304 AHF patients (94.7% belonged to New York Heart Association functional class IV) using gas chromatography. Spearman correlation coefficients were used to examine the associations between the individual and total (the sum of all FFAs) FFAs and clinical and laboratory parameters. After applying a Bonferroni correction to correct for multiple testing, the total FFAs, as well as the individual FFAs (except FFAs 18:0, 20:5, and 22:6), were found to be significantly positively correlated with serum albumin. Only a few additional associations were found: FFA 16:0 was significantly negatively correlated with systolic pulmonary artery pressure, FFA 18:3 was significantly negatively correlated with C-reactive protein and body mass index, and FFA 20:4 was significantly negatively correlated with blood urea nitrogen. Based on our results, we conclude that in patients with severe AHF, individual and total serum FFAs are slightly associated with established laboratory and clinical parameters, which are indicators of heart failure severity.

Keywords: acute heart failure; free fatty acids; gas chromatography

DOI: https://doi.org/10.3390/biomedicines11123197