Leptin resistance in obesity is a condition where excess body fat leads to high levels of the leptin hormone in the blood, but the brain fails to properly respond to leptin's signal to reduce appetite and burn fat. Leptin resistance can occur both centrally in the brain and peripherally in tissues. Potential causes include a failure of leptin to cross the blood-brain barrier and reduced leptin receptor expression interfering with leptin signaling. Treatment focuses on lifestyle changes like diet and exercise to improve leptin sensitivity, as well as drugs that target leptin transport or signaling. Further research is needed to better understand leptin resistance and develop more effective anti-obesity therapies.

1. LEPTIN RESISTANCE IN OBESITY
BY
OWODUNNI, ABRAHAM TOLUWASE
owodunniabraham@gmail.com
University of Ilorin, Ilorin, Nigeria
Department of Biochemistry.
APRIL, 2019. 1

2. OUTLINE
• INTRODUCTION
• OBESITY
• LEPTIN HORMONE
• LEPTIN RESISTANCE
• TREATMENT
• CONCLUSION
• REFERENCES
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3. INTRODUCTION
• Obesity is a chronic disease that represents one of the
most serious global health burdens
• It is associated to an excess of body fat resulting from an
imbalance between energy intake and expenditure
(Sa´inz et al., 2015).
• Leptin, a polypeptide hormone that is produced by
adipocytes in proportion to their triglyceride content, links
changes in body energy (fat) stores to adaptive
responses in the central control of energy balance
(Myers et al., 2009).
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4. OBESITY
• Obesity is a state of excess adipose tissue mass (Flier et al., 2004).
• Obesity level is indicated by:
– Body Mass Index (BMI ≥ 30kg/m 2);
– Waste circumference;
– Waist-to-hip ratio;
– Skinfold Thickness;
– BIA; ETC (Hu, 2008).
• Hormones related to obesity include insulin, leptin, ghrelin, etc (Kaur and
Zhang, 2005 ).
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5. LEPTIN HORMONE
• Leptin is a protein that’s made in the fat cells, circulates in the bloodstream, and
goes to the brain (Frederich et al.,1995).
• The more fatty tissue mass (body fat) you have, the more leptin is produced (Fig. 1)
(Frederich et al.,1995).
Fig. 1: Concept of leptin functioning
Source: Healthjade (2018) 5

6. Fig. 2: General function of Leptin
Source: Healthjade (2018)
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FUNCTION OF LEPTIN

7. MECHANISM OF ACTION
• Leptin is transported to the brain and its effects are mediated by
binding to its receptor (ObR).
• Leptin binding to ObRb induces a series of intracellular signaling
cascades as in seen Figure 4 (Sa´inz et al., 2015).
7Fig 3: Mechanism of leptin action
Source: Sa´inz et al. (2015) 7

8. LEPTIN RESISTANCE
• Leptin resistance is usually used to define states of
hyperleptinemia and lack of response to the hormone
(Healthjade, 2018).
• Leptin resistance can be classified as:
– Central leptin resistance; and
– Peripheral leptin resistance (Shinsuke et al., 2006).
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9. MECHANISMS OF LEPTIN RESISTANCE
The mechanisms of leptin resistance are unclear, but several
possibilities have been postulated (as in Fig. 4):
– A failure of the hormone to cross the BBB and to act on its
target neurons (Caro et al.,1996);
– A reduction in the expression of leptin receptors;
– Failure on the leptin signaling pathway at central and peripheral
levels (Martin et al., 2000).
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Fig. 4: Mechanism of leptin resistance
Source: Sa´inz et al. (2015)

11. TREATMENT
• Improve your diet
– eat whole grains, low caloric diets and observe
intermittent fasting,
• Go for longer aerobic workouts.
– Aerobic exercise can burn fat, reduce body mass, and
increase leptin sensitivity.
• Increase of leptin transport across the blood–brain
barrier or median eminence (Roujeau et al., 2014).
• Use of drugs e.g Metreleptin: metreleptin reverses the
metabolic abnormalities that are seen in lipodystrophy
(Simha, 2014).
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12. CONCLUSION
Increased prevalence of obesity in the world nowadays is
an actual health issue. Unfortunately, the available drugs of
agents for obesity treatment are not fully satisfying.
An advance of science in revealing mystery on mechanism
of leptin resistance is very useful to provide a new molecule
target for anti-obesity agents.
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