Sleeve gastrectomy protects lean mice from future obesity.

Area of Science:

• Metabolic disease and aging research
• Gastroenterology and microbiome studies
• Surgical interventions and longevity

Background:

• Obesity and metabolic diseases accelerate aging and shorten lifespan.
• While dietary interventions show promise, they are often unsustainable for humans.
• Bariatric surgery, specifically sleeve gastrectomy (SG), is an effective metabolic intervention linked to increased lifespan, but its precise mechanisms remain unclear.

Purpose of the Study:

• To investigate if sleeve gastrectomy (SG) confers longevity benefits beyond weight reduction.
• To determine if SG induces surgery-specific metabolic reprogramming.
• To explore the role of the gut microbiome in SG's metabolic effects.

Main Methods:

• A lean mouse model (C57BL/6J) underwent sleeve gastrectomy (SG) or sham operation.
• Mice were fed a low-fat diet and subsequently challenged with a high-fat diet (HFD) in midlife.
• Key metabolic parameters, body composition, energy expenditure, liver histology, adipose tissue inflammation, and cecal microbiome were assessed.

Main Results:

• SG mice showed improved glucose tolerance and insulin sensitivity, even before HFD challenge.
• Post-HFD, SG mice exhibited enhanced metabolic flexibility, increased energy expenditure, and reduced weight gain and adiposity.
• SG led to reduced liver fat accumulation, decreased visceral adipose tissue inflammation, and distinct gut microbiome remodeling with Lactobacillus enrichment.

Conclusions:

• Early-life SG provides lasting metabolic protection against aging-related decline, independent of weight loss.
• Surgery-induced gut microbiome alterations, particularly Lactobacillus enrichment, are potential mechanisms for these benefits.
• Targeting the gut microbiome may offer new therapeutic strategies for metabolic disease and aging.