Tag Archives: leptin

Leptin Deficiency and Early-Onset Extreme Obesity

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A brief report (NEJM 2015; 372: 48-54) details a case of 2.5 year old who weighed 33.7 kg (>99.9% and z score of 7.2) and had BMI of 38.6 (>99.9% and z score of 5.8).

Link to article (and picture/growth curve)

The authors determined that he had a mutation which caused biologically inactive leptin.  Subsequently, treatment with metreleptin injections, improved eating behavior and resulted in substantial weight loss.

Key points:

  • “Current clinical recommendations advise that leptin serum concentrations be measured in children who have rapid weight gain in the first months of life.” (“The severely obese patient –a genetic work-up.” Nat Clin Pract Endocrinol Metab 2006; 2: 172-7)
  • This case report demonstrates that normal circulating levels of the hormone “do not rule out disease-causing mutations in the gene encoding leptin.”

Related blog posts:

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Could Cysteamine help NAFLD?

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Maybe (J Pediatr 2012; 161: 639-45, editorial p 579).

Cysteamine bitartrate has been used in cystinosis and reduces intralysosomal Cys accumulation.  It has potential antioxidant and antiapoptotic effects.  A pilot study has shown that cysteamine may improve NAFLD through unclear mechanisms and may reduce aminotransferase levels in the serum along with increasing adiponectin levels (reduced in NAFLD).

Adiponectin is produced by adipocytes and helps regulate glucose and lipid homeostasis.  It has insulin-sensitizing properties as well as anti-inflammatory effects. Adiponectin levels inversely correlate with degree of obesity and insulin resistance.

In this study of 10 children with biopsy-proven NAFLD, cysteamine therapy was administered for 24 weeks.

  • Following therapy, multimers of adiponectin were increased and total adiponectin level increased 49.3% (P = 0.05).
  • ALT dropped from a mean of 123 IU/L at baseline to 55 IU/L at 24 weeks.
  • AST dropped from a mean of 61 IU/L at baseline to 32 IU/L at 24 weeks.
  • Adiponectin values returned to baseline 16 weeks after completing treatment while aminotransferase values remained low.

The editorial notes that an NIH-funded NASH clinical research network study will investigate cysteamine in a much larger cohort.

Related blog entries:

Lower leptin with physical activity

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Leptin is a cytokine expressed primarily by adipose tissue and helps regulate energy homeostasis in the body.  Higher leptin levels are found in obesity and associated with an increase risk of cardiovascular disease, insulin resistance, and type 2 diabetes.  In a recent study, physical activity, especially vigorous physical activity, has been shown to be negatively associated with leptin levels (J Pediatr 2012; 160: 598-603).

This study was conducted in school settings in 10 European cities from 9 countries (n=902) with ages 12-18 years.  Several fitness tests including handgrip, long jump, and shuttle runs were measured along with serum fasting leptin, insulin, and glucose.

Vigorous activity and fitness test results were associated with lower leptin levels; these findings were maintained when controlling for confounders.  It is not known the exact mechanisms whereby physical activity can lower leptin levels as this finding is independent of total body fat.  The authors note that previous studies have shown some contradictory results; the authors note that this could be related to drawbacks in how some studies measured physical activity.

This study’s information, when combined with previous studies (see below) on hormonal adaptations with weight loss, suggest a reason why exercise is important to maintain weight loss.  Losing weight without exercise could result in increased appetite and make it more difficult to achieve long-term results.  In contrast, physical activity may help maintain weight loss by improving hormonal adaptation.

Additional references:

  • -NEJM 2011; 365: 1597.  Persistence of hormonal adaptations with weight loss.  Due to persistent changes in hormones like leptin & peptide YY, hard to keep wt off -result is increased appetite.
  • -NEJM 2009; 360: 859.  Obesity-wt loss: composition of diet does not seem to be important.  Total calories important.
  • -NEJM 2007; 356: 237.  Leptin receptor deficiency present in 3% of 300 patients with early-onset obesity and hyperphagia.
  • -Pediatrics 2007; 120: suppl 4: S164-S287.
  • -NEJM 2007; 357: 370.  Obestiy spread in social network.
  • -Gastroenterology 2007; 132: 2085-2276.  Special issue on obesity issues.
  • -NEJM 2006; 355: 1593.  Case review on obesity c DDx and mgt.