Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

Area of Science:

• Metabolic disorders and epigenetics
• Renal pathophysiology
• Pharmacological interventions

Background:

• High-fat diet (HFD) induces metabolic memory by altering histone modifications (H3K36me2 and H3K27me3) on the FOXO1 gene promoter.
• HFD-induced metabolic memory is linked to insulin resistance and potential renal damage.

Purpose of the Study:

• To investigate if diet reversal combined with metformin can overcome HFD-induced metabolic memory and renal damage.
• To assess the effects of metformin and diet reversal on biochemical, histological, and physiological markers of insulin resistance and kidney function.

Main Methods:

• Adult Sprague-Dawley rats were fed a HFD for 16 weeks to induce insulin resistance.
• Subsequent treatment involved diet reversal alone or with metformin for 8 weeks.
• Evaluated blood glucose, lipids, kidney function markers (BUN, creatinine), blood pressure, vascular reactivity, and kidney histology.

Main Results:

• Diet reversal alone improved lipid profiles but did not prevent renal complications.
• Metformin with diet reversal normalized blood glucose, lipids, BUN, and creatinine levels.
• Metformin activated AMP-activated protein kinase (AMPK), reduced inflammatory and apoptotic markers in the kidney, lowered blood pressure, and attenuated kidney fibrosis and glomerulosclerosis.

Conclusions:

• Metformin treatment, in conjunction with diet reversal, effectively overcomes HFD-induced metabolic memory.
• This combination therapy prevents HFD-induced renal damage, offering a potential therapeutic strategy for metabolic syndrome-related kidney disease.