Diabetic Remission Linked to FGF-19 Levels in Bariatric Surgical Patients

Elevated serum levels of the recently identified hormone fibroblast growth factor 19 (FGF-19), a gut hormone, were found to be associated with both improved mitochondrial health and overall diabetic remission in women receiving bariatric surgery.

Lucia Martinez de la Escalera, a PhD candidate with the Warwick School of Medicine (pictured), and colleagues concluded that changes in FGF-19 levels in women receiving biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) could highlight the importance of FGF-19 in association with mitochondria in adipose tissue (AT) during diabetic remission.

Martinez de la Escalera points out that the inability of AT to cope with over-nutrition "whilst maintaining important metabolic and endocrine functions" is a key factor in the development of metabolic syndrome and type-2 diabetes mellitus (T2D).

Mitochondria are vital to metabolic health and "nutrient-induced mitochondrial dysfunction" can lead to insulin resistance and development of T2D, both of which can be "reduced through bariatric surgery," per an article published in BioMed Central.

The connection between bariatric surgery and diabetic remission is well-known, according to Martinez de la Escalera and colleagues, who point out that bariatric surgery has been proven to have "significantly greater success rates than pharmacological, exercise, and diet interventions."

However, Martinez de la Escalera and colleagues believe that surgery alone, which reduces stomach volume and nutrient absorption capacity, cannot "fully explain the profound weight loss and metabolic improvement observed after these surgeries versus medical/lifestyle interventions."

Martinez de la Escalera turned to the recently identified ileal-derived hormone FGF-19, an enterokine regulator which affects glucose, lipids, bile acids, and nutrient metabolism, as potentially involved in post-bariatric surgery metabolism improvements.

The study included 39 Caucasian women with T2D and body mass greater than 35 kg/m². The study participants were undergoing BPD (n=12), LGCP (n=15), or LAGB (n=12) at Prague's OB Clinic. Baseline blood, biochemistry, and body composition analyses were completed prior to surgery, and at 6 months post-surgery following 10-hour overnight fasts.

DNA and RNA were extracted from frozen AT collected before surgery and at the 6-month mark and assayed for expression and mitochondrial number, and measurements of serum FGF-19 levels were taken via enzyme-linked immunosorbent assay (ELISA).

The resulting data showed that although all 39 patients in the study saw significantly improved body weight (avg. 22.73% excess weight loss), as well as improvements in serum hemoglobin A1c (HbA1c) (avg. 82.5% change) and homeostatic model assessment of insulin resistance (HOMA-IR) levels (avg. 58.07% change), the 12 patients who received BPD exhibited greater weight loss (avg. 30.67% excess weight loss), greater reductions to serum total cholesterol (24%), serum LDL cholesterol (29%) and improvement in serum HDL cholesterol (15% increase from pre-surgery) than patients receiving LGCP and LAGB.

Martinez de la Escalera and colleagues noted that post-surgery FGF-19 levels showed significant differences across all three procedures. FGF-19 increased in a majority of LGCP (73%) and BPD (58%) patients, but increased in only 17% of LAGB patients, with the highest numbers of post-surgery changes to FGF-19 levels inversely correlated with changes in mitochondrial number in white AT across all 39 patients.

Martinez de la Escalera notes that the only other correlation between changes in mitochondrial number in white AT (-0.400, P=0.023) was in relation to total cholesterol numbers (which improved by an average of 11.13 mmol/L as mitochondrial numbers rose).

The researchers theorize that the inverse correlation between FGF-19 levels and mitochondrial numbers "may be interpreted as a shift towards a less fragmented and more elongated mitochondrial network when FGF-19 levels are raised."

Martinez de la Escalera points out that in previous studies, mitochondrial fragmentation has been "associated with apoptosis," increased cytokine production, and impaired insulin signaling. Fragmentation of muscle mitochondria, Martinez de la Escalera writes, "has been reported in several mouse and human models of obesity and type-2 diabetes."

The study's initial hypothesis that FGF-19 levels were associated with improved metabolic health outcomes post-bariatric surgery was confirmed by data and highlighted direct associations between FGF-19 levels and mitochondrial improvement to varying degrees across the three bariatric surgical procedures (BPD, LGCP, LAGP) with the greatest benefits noticed inpatients receiving BPD.

The researchers concluded that FGF-19 levels "associated with improved mitochondrial health in AT" do lead to "greater control of mitochondrial gene regulation and overall type-2 diabetes remission." The discovery of the connections between FGF-19 and mitochondria in AT, researchers hope, will lead to further study of FGF-19's potential as a target for diabetic recovery treatments leading to diabetic remission.

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