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Completed

NCT Number: NCT07806448

Impact of Asprosin and Neuregulin 4 on Metabolic Parameters, Anthropometric Indices and Body Composition After Laparoscopic Sleeve Gastrectomy

Asprosin and neuregulin 4 (NRG4) sit on opposing arms of adipose endocrine physiology. Asprosin is a fasting-induced, white adipose-derived glucogenic and orexigenic hormone that rises with adiposity and insulin resistance. NRG4 is a brown and beige adipose-derived, anti-lipogenic and hepatoprotective factor that falls with adiposity. Both have been examined separately after metabolic and bariatric surgery, but never in the same cohort, and existing surgical data cannot separate a weight-loss-dependent effect from an effect of the operation itself.

Objectives: To quantify the change in fasting serum asprosin and NRG4 over twelve months after laparoscopic sleeve gastrectomy (LSG); to determine whether those changes are associated with metabolic improvement independently of weight loss; and to characterise their relationship with anthropometric indices and body composition.

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Key information

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Observational

Primary location

The surgical department of Medical Research Institute Hospital, Alexandria University

Alexandria, 21531, Egypt

About this study

Adipose tissue is an endocrine organ whose secretory profile changes profoundly after metabolic and bariatric surgery. Two of its products have attracted attention for opposite reasons, and the relationship between them has never been examined in a surgical population.

Asprosin is the C-terminal cleavage product of profibrillin, encoded by the two terminal exons of FBN1 and released principally by white adipose tissue. Its discovery established it as a fasting-induced glucogenic hormone acting on the hepatocyte through a cyclic AMP-protein kinase A pathway. It was subsequently shown to cross the blood-brain barrier and activate orexigenic AgRP neurons, thereby stimulating appetite and adiposity accrual. Two receptors have been described: the olfactory receptor OLFR734 for the hepatic glucogenic arm and protein tyrosine phosphatase receptor delta for the central orexigenic arm [4]. In humans, circulating asprosin is consistently higher in obesity, insulin resistance, type 2 diabetes and metabolic syndrome, and a meta-analysis across these conditions confirms the association. Interventions that reduce adiposity lower it.

Neuregulin 4 is an epidermal growth factor family ligand of ErbB4, enriched in brown and beige adipose tissue and secreted as an endocrine signal to the liver. It is reduced in rodent and human obesity and protects against hepatic steatosis by suppressing lipogenesis. Hepatic NRG4 signalling constitutes an endocrine checkpoint governing the transition from simple steatosis to steatohepatitis, NRG4 promotes systemic fuel oxidation and a favourable adipokine profile [11], and exercise induces adipose NRG4 through PPARγ, which then disrupts hepatic cGAS-STING inflammatory signaling. In humans, low circulating NRG4 is associated with metabolic syndrome, subclinical carotid disease and steatotic liver disease in adults and children. The literature is not unidirectional: elevated NRG4 has been reported in diabetes, a meta-analysis of observational studies found no overall case-control difference, and a study with paired hepatic transcriptomic profiling found no difference in steatotic liver disease. This heterogeneity is widely attributed to differences in commercial assay calibration and population, a point that directly shapes the analytical design of the present study.

Only three studies have examined either analyte after metabolic and bariatric surgery. Serum asprosin fell six months after surgery, and pre-operative asprosin was the single independent predictor of six-month excess weight loss. In sleeve gastrectomy, adipose-tissue asprosin was elevated relative to non-obese controls while pre-operative serum asprosin did not discriminate, yet serum asprosin still fell by six months. For NRG4, a single dedicated study found that circulating NRG4 rose during the early post-operative recovery phase, before substantial weight loss, and that Nrg4 knockout blunted the hepatic benefit of sleeve gastrectomy in rodents, establishing the rise as contributory rather than merely correlative.

Four gaps follow. First, the two hormones have never been co-measured in any surgical cohort, so the relationship between the falling glucogenic-orexigenic arm and the rising hepatoprotective arm is uncharacterised. Second, existing surgical data are confined to a pre-operative measurement and a single six-month measurement, which cannot separate a weight-loss-dependent effect from an early effect of the operation. Third, neither analyte has been related to quantified body composition after surgery, only to crude anthropometry. Fourth, post-prandial asprosin dynamics, the physiologically defining feature of the hormone, have never been examined before and after a bariatric operation.

ASPEN-SG is designed to address these gaps. This paper reports the protocol.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • body mass index of at least 35 kg/m² regardless of the presence
  • absence or severity of obesity-related comorbidities
  • should be considered at 30-34.9 kg/m² in the presence of metabolic disease

Exclusion criteria

  • revisional or emergency surgery
  • type 1 diabetes or insulin-treated type 2 diabetes
  • use within three months of a GLP-1 receptor agonist
  • dual GIP/GLP-1 receptor agonist
  • SGLT2 inhibitor or thiazolidinedione
  • systemic corticosteroid or immunosuppressive therapy
  • chronic liver disease of non-metabolic aetiology or cirrhosis
  • alcohol intake above 20 g/day in women or 30 g/day in men
  • estimated glomerular filtration rate below 60 mL/min/1.73 m²
  • FBN1-related connective tissue disorder
  • active or recent malignancy
  • untreated thyroid
  • adrenal or gonadal disorder
  • pregnancy or lactation
  • any device precluding bioelectrical impedance analysis
  • high-sensitivity C-reactive protein above 10 mg/L at baseline

Treatment and study plan

Sleeve gastrectomy

Procedure

Greater curvature devascularisation commences 4-6 cm proximal to the pylorus and extends to the angle of His with complete fundal mobilisation; gastric transection is performed over a 36-40 Fr calibration bougie; staple-line reinforcement policy.

Primary outcomes

  1. log-transformed fasting serum asprosin and NRG4

    Time frame: 6 months

    within-participant change from baseline in log-transformed fasting serum asprosin and NRG4

  2. HOMA-IR

    Time frame: 6 months

    the association of the change from baseline in log-transformed fasting serum asprosin and NRG4 with the change in HOMA-IR, independently of percentage total weight loss.

    The Formula: It multiplies fasting glucose by fasting insulin and divides by a constant (22.5 when glucose is in mmol/L, or 405 when in mg/dL).

    Less than 1.0: Optimal insulin sensitivity (low resistance). 1.0 to 1.9: Normal range. 2.0 to 2.9: Early insulin resistance. 3.0 or higher: Moderate to significant insulin resistance, raising the risk for pre-diabetes or type 2 diabetes.

Secondary outcomes

  1. early-phase change

    Time frame: at day 7 and at 1 month

    within-participant change from baseline in log-transformed fasting serum asprosin and NRG4.

  2. anthropometry

    Time frame: at day 7, 1 month, 3 months, 6 months and 12 months

    Weight is measured to 0.1 kg on a calibrated platform scale in the morning after the fasting draw. Waist and hip circumferences are the mean of three readings, with a fourth taken if the range exceeds 1 cm. Two trained observers perform all anthropometry; inter-observer reliability is established before enrolment and an intraclass correlation below 0.95 for any circumference requires retraining.

  3. body composition

    Time frame: at day 7, 1 month, 3 months, 6 months and 12 months

    Body composition is measured on a single InBody 120 segmental analyser (InBody Co. Ltd., Seoul, South Korea) for the entire study, the platform used in this group's published body-composition work, which preserves comparability with that cohort. Measurement is standardised to the morning, fasting, post-void state with no exercise for 12 hours, no alcohol for 24 hours, light clothing, bare feet, and the same room and device at every visit. Recorded variables are body fat mass and percentage, body muscle mass and percentage, fat-free mass, skeletal muscle mass, visceral fat, total, intracellular and extracellular water, and the derived fat mass index, fat-free mass index, skeletal muscle mass index and the proportion of weight lost as fat-free mass.

  4. TyG index

    Time frame: at day 7, 1 month, 3 months, 6 months and 12 months

    The Triglyceride-Glucose (TyG) index is a simple, reliable blood marker used to measure insulin resistance and cardiometabolic risk.

    Normal and High-Risk Ranges:

    Optimal: A TyG index under 4.49 (using specific standard scales) or lower values generally point to healthy metabolic function.

    Insulin Resistance: Values above standard cutoffs (often varying by population, with high risk frequently cited at ≥ 8.77 or ≥ 9.04 depending on the specific diagnostic calibration) suggest the body is struggling to process insulin properly.

  5. lipid profile

    Time frame: at day 7, 1 month, 3 months, 6 months and 12 months

    A lipid profile is a blood test that measures the amount of cholesterol and fats in your blood to check your risk for heart disease.

    Total Cholesterol: The overall amount of cholesterol in your blood. A normal level is below 200 mg/dL.LDL (Low-Density Lipoprotein): The "bad" cholesterol that can block your blood vessels. A normal level is below 100 mg/dL.HDL (High-Density Lipoprotein): The "good" cholesterol that helps clear bad cholesterol away. A higher level (above 60 mg/dL) protects your heart.Triglycerides: A type of fat stored for energy. A normal level is below 150 mg/dL.VLDL (Very Low-Density Lipoprotein): A type of bad fat that carries triglycerides. A normal level is below 30 mg/dL.

  6. AST/ALT ratio

    Time frame: at day 7, 1 month, 3 months, 6 months and 12 months

    The AST/ALT ratio (also called the De Ritis ratio) compares two liver enzymes in your blood to help doctors find the cause of liver or muscle damage.

    Less than 1.0: ALT is higher than AST. This is common in metabolic fatty liver stress or viral hepatitis.

    Around 1.0 to 1.2: AST and ALT are balanced or slightly raised together, which can happen with early liver stress or viral infections.

    1.2 to 2.0: AST is higher than ALT. This can point to advanced liver scarring (fibrosis), cirrhosis, or recent intense exercise.

    Greater than 2.0: AST is more than double ALT. This strongly suggests alcohol-related liver injury or alcoholic hepatitis.

    Non-liver causes: Because AST is also found in heart and skeletal muscles, high AST (and a high ratio) can happen after severe muscle damage or a heart event.

  7. high-sensitivity C-reactive protein

    Time frame: at day 7, 1 month, 3 months, 6 months and 12 months

    hs-CRP (high-sensitivity C-reactive protein) is a blood test that measures low levels of inflammation in the body to help assess your risk of heart disease.

    Results are measured in milligrams per liter (mg/L):

    Low risk: Less than 1.0 mg/L Average or moderate risk: 1.0 to 3.0 mg/L High risk: Above 3.0 mg/L Very high (above 10 mg/L): Usually points to a current infection or acute injury rather than long-term heart risk.

  8. leptin

    Time frame: at day 7, 1 month, 3 months, 6 months and 12 months

    Leptin is a hormone made mostly by fat cells that helps your body manage energy balance and long-term appetite.

    Males (Normal BMI): [0.5 to 12.5 nanograms per milliliter (ng/mL)](0.6.1, 0.6.2) Females (Normal BMI): [0.5 to 15.2 ng/mL](0.6.1, 0.6.2) (women often show higher levels than men at comparable body fat due to estrogen effects).

    Obese Individuals (Any Sex): Typically range from 20 to 100+ ng/mL, which often reflects a leptin resistance pattern rather than simple excess.

    Deficient Levels: Below 0.5 ng/mL can indicate true deficiency or severe malnutrition/over-dieting

  9. adiponectin

    Time frame: at day 7, 1 month, 3 months, 6 months and 12 months

    Adiponectin is a protective protein hormone secreted by fat tissue that helps regulate glucose levels, break down fatty acids, and lower systemic inflammation.

    Normal Range: Typically ranges from 5 to 37 µg/mL depending on your body mass index (BMI) and sex.

    Low Levels: Connected to obesity, type 2 diabetes, metabolic syndrome, and heart disease.

  10. ghrelin

    Time frame: at day 7, 1 month, 3 months, 6 months and 12 months

    Ghrelin is a peptide hormone produced mainly by the stomach that signals your brain to stimulate appetite and increase food intake.

    The normal reference range for total ghrelin in plasma typically spans from 100 to 1,200 pg/mL in healthy adults, though specific values change based on whether you are fasting or have recently eaten:

    Fasting state: Levels rise to stimulate hunger, often ranging between 500 and 2,500 pg/mL.

    Postprandial state (after eating): Levels drop significantly, usually falling between 100 and 900 pg/mL.

    Normal-weight controls: Specific reference panels often cite a baseline fasting range of 520 to 700 pg/mL.

Sponsors and collaborators

Lead sponsor

General Committee of Teaching Hospitals and Institutes, Egypt

Other Gov

Registry information

Official study title

The Impact of Asprosin and Neuregulin 4 on Metabolic Parameters, Anthropometric Indices and Body Composition After Laparoscopic Sleeve Gastrectomy: Protocol for a Prospective Longitudinal Cohort Study With a Non-obese Reference Group and a Nested Mixed-meal Sub-study (ASPEN-SG)

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Sep 8, 2026
Registry last updated
Sep 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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