Hormonal
In obese individuals, chronically elevated leptin levels induce leptin resistance through impaired blood-brain barrier transport and central receptor signaling deficits, rendering exogenous leptin therapy ineffective for weight loss.
If you are obese, your body likely already has high levels of leptin, but your brain has stopped listening to it (leptin resistance). Therefore, taking leptin supplements or injections will not help you lose weight. The focus should be on improving metabolic sensitivity rather than adding more hormone.
Chronically raised leptin levels which characterize obesity decrease the transport of leptin into the CNS and impair the signaling properties of leptin receptors. The resulting resistance to leptin confers increased susceptibility to diet-induced obesity, which in turn raises leptin levels further and worsens existing leptin resistance leading to a vicious cycle of weight gain.
Why this rating
The paper is a comprehensive review citing multiple human and rodent studies, though it acknowledges unresolved questions in humans.
Source
Leptin and the Control of Body Weight: A Review of Its Diverse Central Targets, Signaling Mechanisms, and Role in the Pathogenesis of Obesity
Ashwini Oswal et al. · Obesity · 2009
DOI 10.1038/oby.2009.228
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- Leptin regulates energy homeostasis not only by acting as a satiety signal in the arcuate nucleus but also by modulating synaptic plasticity and reward perception in extrahypothalamic areas like the ventral tegmental area and striatum.Good
- Leptin resistance in obesity is driven by impaired transport of leptin across the blood-brain barrier, largely due to saturation by high endogenous levels and inhibition by hypertriglyceridemia.Good
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