What is the clinical evidence from this study?

Study design: Observational. Population: Healthy volunteers (n=24). Intervention: Fasting vs. Fed state (2 hours after standardized meal). Primary outcome: ANGPTL4 mRNA expression in subcutaneous adipose tissue (+90% increase, p=<0.001).

June 3, 2020Open Access

Fasting induces ANGPTL4 and reduces LPL activity in human adipose tissue

Q: What are the key findings of this study?

Fasting for 24 hours significantly increased ANGPTL4 mRNA by 90% and decreased LPL activity by 60% in human subcutaneous adipose tissue.

Resultado clave

Fasting for 24 hours significantly increased ANGPTL4 mRNA by 90% and decreased LPL activity by 60% in human subcutaneous adipose tissue.

Diseño del estudio

Tipo

Observational (n=24)

Multicéntrico

PICO estructurado

Does a prolonged 24-hour fast increase ANGPTL4 expression and reduce LPL activity in human subcutaneous adipose tissue?

Población

24 healthy volunteers aged 40-70 years (median age 55 years) with a BMI of 22-30 kg/m2 (median BMI 25 kg/m2).

Intervención

24-hour prolonged fast (standardized meal consumed at 18:00 h, followed by fasting until 20:00 h the next day).

Comparador

Baseline fed state (blood and adipose tissue biopsy taken 2 hours after the standardized meal).

Resultado

Effect of a prolonged fast on ANGPTL4 and LPL gene and protein expression in human subcutaneous adipose tissue.surrogate

Fasting increases ANGPTL4 levels in human adipose tissue, likely driven by increased cortisol and free fatty acids and decreased insulin, which subsequently reduces LPL activity.

Resultado numérico

Estimación del efecto: +90% increase

valor p: p=<0.001

Limitaciones

Cannot demonstrate a direct causal link between the upregulation of ANGPTL4 in human adipose tissue during fasting and the decrease in LPL activity.
Unable to visualize LPL protein in the human primary adipocytes.

Resumen

OBJECTIVE: Studies in mice have shown that the decrease in lipoprotein lipase (LPL) activity in adipose tissue upon fasting is mediated by induction of the inhibitor ANGPTL4. Here, we aimed to validate this concept in humans by determining the effect of a prolonged fast on ANGPTL4 and LPL gene and protein expression in human subcutaneous adipose tissue. METHODS: Twenty-three volunteers ate a standardized meal at 18.00 h and fasted until 20.00 h the next day. Blood was drawn and periumbilical adipose tissue biopsies were collected 2 h and 26 h after the meal. RESULTS: Consistent with previous mouse data, LPL activity in human adipose tissue was significantly decreased by fasting (-60%), concurrent with increased ANGPTL4 mRNA (+90%) and decreased ANGPTL8 mRNA (-94%). ANGPTL4 protein levels in adipose tissue were also significantly increased by fasting (+46%), whereas LPL mRNA and protein levels remained unchanged. In agreement with the adipose tissue data, plasma ANGPTL4 levels increased upon fasting (+100%), whereas plasma ANGPTL8 decreased (-79%). Insulin, levels of which significantly decreased upon fasting, downregulated ANGPTL4 mRNA and protein in primary human adipocytes. By contrast, cortisol, levels of which significantly increased upon fasting, upregulated ANGPTL4 mRNA and protein in primary human adipocytes as did fatty acids. CONCLUSION: ANGPTL4 levels in human adipose tissue are increased by fasting, likely via increased plasma cortisol and free fatty acids and decreased plasma insulin, resulting in decreased LPL activity. This clinical trial was registered with identifier NCT03757767.

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