Fragment 176-191

Overview

HGH Fragment 176-191 represents the C-terminal 16-amino-acid sequence (amino acids 176-191) of human growth hormone. This modified fragment retains the potent lipolytic (fat-burning) action of native HGH while eliminating its proliferative and insulin-antagonistic effects.

The fragment was developed to isolate HGH's fat-metabolizing properties without the growth-promoting effects that could be problematic in certain research contexts. It represents a targeted approach to studying HGH's metabolic actions.

Molecular Structure

The fragment maintains the structural elements responsible for lipolytic activity while lacking the regions involved in growth promotion.

Mechanism of Action

Beta-Adrenergic Signaling

Fragment 176-191 works through selective receptor activation:

1. Beta-3 Adrenergic Receptor (ADRB3) Binding

   • Expressed primarily in white and brown adipose tissue
   • Activation increases intracellular cAMP levels
   • Does not use classical growth hormone receptors

2. PKA Activation

   • Protein Kinase A (PKA) initiated by cAMP elevation
   • Triggers downstream lipolytic signaling cascades
   • Phosphorylates hormone-sensitive lipase

3. Thermogenesis Stimulation

   • ADRB3 stimulation linked to mitochondrial uncoupling
   • Enhanced thermogenesis in skeletal muscle
   • Increased basal metabolic rate

Lipid Metabolism Effects

• Lipolysis Enhancement: Stimulates breakdown of stored triglycerides
• Lipogenesis Inhibition: Reduces new fat cell formation
• Fatty Acid Oxidation: Increases fat utilization for energy
• Selective Action: Targets stubborn abdominal fat deposits

Key Research Findings

AOD9604 Clinical Trial (2004)

A clinical trial examining HGH Fragment 176-191 (study AOD9604) found:

• Highly successful stimulation of body fat metabolism
• Three-month study at six different doses
• Key finding: Lowest daily dose (1 mg) was most effective
• Suggests non-linear dose-response relationship

Animal Studies

In a 14-day study with overweight mice:

• Boosted skeletal muscle thermogenesis
• Accelerated fat burning
• Increased beta(3)-AR RNA (ADRB3) levels
• Rapid weight reduction in obese animals
• No effect on lean mice (suggesting selective action)

Safety Profile

Six randomized, double-blind, placebo-controlled studies indicate:

• No harmful effects on carbohydrate metabolism
• No insulin resistance development
• No decreased glucose tolerance
• No increased IGF-1 levels
• No proliferative effects on bone or organ tissue

Comparison with Full HGH

Differences from AOD-9604

Fragment 176-191 and AOD-9604 are often confused:

• AOD-9604 is a modified version of Fragment 176-191
• AOD-9604 has a tyrosine substitution for stability
• Both target similar pathways
• AOD-9604 has more clinical trial data

Research Applications

Obesity Research

The fragment provides a tool for studying:

• HGH's fat-metabolic effects in isolation
• Beta-adrenergic signaling in adipose tissue
• Thermogenesis mechanisms
• Lipolysis without growth effects

Metabolic Syndrome

Potential research areas:

• Fat mass reduction without lean mass effects
• Metabolic improvement without glucose impairment
• Selective adipose tissue targeting

Important Considerations

While Fragment 176-191 shows promise in research:

• Human evidence remains extremely limited
• Effects in humans appear modest
• Requires combination with diet/exercise for measurable outcomes
• Not a standalone fat-loss solution

Regulatory Status

Fragment 176-191 is a research compound not approved for human therapeutic use. AOD-9604 (the modified version) has undergone more extensive clinical development.

References

Key sources include the Journal of Endocrinology, AOD9604 clinical trial publications, and research on beta-adrenergic receptor signaling in adipose tissue.