Where is leptin synthesized

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Current Diabetes Reports 3 — Journal of Endocrinology R11 —R Biology of Reproduction 70 — Sign in Create account. Author guidelines Submit now Reasons to publish Ethical policy Open-access policy Publication charges Author resource centre. Advanced Search Help. Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity in Reproduction. Free access. Download PDF. Check for updates. Get Permissions. Abstract A series of epidemiological, clinical and experimental studies have shown that there are associations between the fetal and neonatal nutritional environment and the amount and distribution of adipose tissue in adult life.

Introduction Currently more than half of all adults in the United States and the United Kingdom are either overweight i. Birth weight and adult obesity The relationship between birth weight and fatness, measured in childhood or adulthood, is generally positive, although a number of studies have reported that there is a J-shaped or U-shaped relationship between birth weight and adult fat mass, with a higher prevalence of obesity occurring at both low and high birth weights Maffeis et al.

Early nutrition and programming of adipose tissue and leptin synthesis and secretion in the human In the human infant, there is a positive relationship between cord blood concentrations of leptin at delivery and birth weight or neonatal adiposity. Leptin synthesis and secretion before birth In rodents, the capacity of fetal adipocytes to synthesise leptin is relatively limited until late in gestation and, while the placenta synthesises little if any leptin Kawai et al.

Maternal undernutrition and the regulation of maternal and fetal plasma leptin concentrations In sheep, the impact of maternal undernutrition on plasma leptin concentrations appears to be dependent on the breed and age of the ewe and on the level of nutrient restriction. At this time, the mechanisms responsible for regulating leptin expression in adipocytes are unknown. It is likely that a number of hormones modulate ob gene expression, including glucocorticoids and insulin.

Mice with inactivating mutations in the gene encoding leptin or its receptor have indistinguishable, recessive phenotypes of obesity, with roughly three times the body weight and five times the fat mass of normal mice. They also manifest diabetes, and show cold intolerance, depressed immune function and infertility. Mutations in ob or db genes appear to be a very rare cause of morbid obesity in humans, but both have been described.

The effect of such mutations on body weight is dramatic. The figure to the right depicts the growth curve for a young girl found to have homozygous inactivating mutations of the ob gene, contrasted to normal children 2nd to 98th percentiles. One other disease associated with leptin deficiency is lipodystropy, a condition with multiple causes that is characterized by loss of adipose tissue. Importantly, blood concentrations of leptin are elevated in a majority of obese humans, especially those with diet-induced obesity.

Moreover, treatment of such individuals with leptin is not effective in reducing obesity, which makes sense because they already have high levels of endogenous leptin.

High blood levels of leptin in the face of obesity indicates what is called leptin resistance. The mechanisms for such resistance are poorly understood and likely involve multiple defects in leptin signal transduction within the central nervous system.

Is leptin useful for treating human obesity? In those rare cases where leptin is actually deficient due to mutations in the ob gene, leptin treatment is effective and life preserving. Leptin is also useful for treating some patients with lipodystrophy. Thus, secretions of the brain may derive from brain supportive structures as well as from neurons. They exit by way of both fenestrated endothelia in the arachnoid villi 42 and perineuronal channels that communicate between the subarachnoid space and interstitial spaces in the retroperitoneum and the nasopharyngeal submucosa In contrast to the tightly controlled and restricted entry of substances into the brain determined by the blood-brain barrier, the pathways of exit are unrestricted by molecular size and are not regulated by specific transport systems.

Thus, leptin, a peptide approximately 16 kD in size, and other molecules, if synthesized in brain whether by neurons or by other supportive tissues, can readily become secretions of the brain if they gain entry to the cerebrospinal fluid. Presence of leptin mRNA in rat brain and glioblastoma cells was documented by PCR and leptin protein identified by immunohistochemistry. Leptin gene expression in rat brain. San Diego, California. Scharrer E , Scharrer B. Research Nervous and Mental Disease.

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