Developmental Changes inobGene Expression and Circulating Leptin Peptide Concentrations

Devaskar, Sherin U.; Ollesch, Claudia; Rajakumar, Rosario A.; Rajakumar, Premeela A.

doi:10.1006/bbrc.1997.7237

Cited by 107 publications

(71 citation statements)

References 25 publications

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“…This is in agreement with previous observations that BAT is an important source of serum leptin at early stages of development (24). Interestingly serum insulin levels are increased in TGϩ, ␣Ϫ͞Ϫ animals despite normal glucose levels, which could be an indication of peripheral insulin resistance.…”

Section: Discussionsupporting

confidence: 93%

C/EBPα is required for differentiation of white, but not brown, adipose tissue

Linhart

Ishimura-Oka

DeMayo

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

294

186

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The transcription factor CCAAT enhancer binding protein ␣ (C͞ EBP␣) is expressed at high levels in liver and adipose tissue. Cell culture studies show that C͞EBP␣ is sufficient to trigger differentiation of preadipocytes into mature adipocytes, suggesting a central role for C͞EBP␣ in the development of adipose tissue. C͞EBP␣ knockout mice die within 7-12 h after birth. Defective gluconeogenesis of the liver and subsequent hypoglycemia contribute to the early death of these animals. This short life span impairs investigation of the development of adipose tissue in these mice. To improve the survival of C͞EBP␣؊͞؊ animals, we generated a transgenic line that expresses C͞EBP␣ under the control of the albumin enhancer͞promoter. This line was bred into the knockout strain to generate animals that express C͞EBP␣ in the liver but in no other tissue. The presence of the transgene improved survival of C͞EBP␣؊͞؊ animals almost 3-fold. Transgenic C͞EBP␣؊͞؊ animals at 7 days of age show an absence of s.c., perirenal, and epididymal white fat despite excess lipid substrate in the serum, whereas brown adipose tissue is somewhat hypertrophied and shows minimal biochemical alterations. Interestingly, mammary gland fat tissue is present and exhibits normal morphology. The absence of white adipose tissue in many depots in the presence of high serum lipid levels shows that C͞EBP␣ is required for the in vivo development of this tissue. In contrast, brown adipose tissue differentiation is independent of C͞EBP␣ expression. The presence of lipid in brown adipose tissue serves as an internal nutritional control, indicating that neither nutritional intake nor lipoprotein composition is likely responsible for the absence of white fat.

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Section: Discussionsupporting

confidence: 93%

C/EBPα is required for differentiation of white, but not brown, adipose tissue

Linhart

Ishimura-Oka

DeMayo

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

294

186

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“…Plasma leptin levels then remained relatively low in the neonate until day 5 before increasing to a transient peak at day 12, and this pattern was comparable in males and females. A similar neonatal pattern of plasma leptin has been reported in both the rat (Rayner et al 1997, Matsuda et al 1999, Morash et al 2001) and the mouse (Devaskar et al 1997, Ahima et al 1998, and a transient peak has also been observed in humans at 3 weeks of age (Harigaya et al 1999). The present work further shows that neonatal leptin fluctuations occur on a background of stable but relatively low hypothalamic Ob-Rb mRNA and protein expression, consistent with a previous report showing low hypothalamic Ob-Rb immunolocalisation in the fetal and neonatal rat (Matsuda et al 1999).…”

Section: Discussionsupporting

confidence: 91%

Developmental changes in plasma leptin and hypothalamic leptin receptor expression in the rat: peripubertal changes and the emergence of sex differences

Smith

Waddell

2003

Journal of Endocrinology

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Leptin, the peptide hormone product of the ob gene, regulates food intake and energy expenditure at the hypothalamic level via the long-form of the leptin receptor (Ob-Rb). Leptin also plays a key role in determining the onset of puberty, but there is controversy as to whether leptin provides a trigger for puberty or is a permissive signal. Thus, although leptin administration can advance puberty onset in rodents, circulating leptin appears stable across puberty. While these data suggest a permissive role for leptin in rat puberty, it is possible that a change in hypothalamic response to leptin (e.g. via increased Ob-Rb expression) could enhance leptin action and thus trigger puberty without a rise in circulating leptin. In the present study we assessed developmental changes in hypothalamic Ob-Rb mRNA and protein expression in female and male rats from late fetal to postpubertal life. Quantitative RT-PCR showed that Ob-Rb mRNA increased (P<0·05) by around fivefold from fetal to postpubertal life in both females and males. These increases in Ob-Rb mRNA expression were gradual, but did not increase significantly between postnatal day 30 (pre-puberty) and day 51 (post-puberty). By day 51, hypothalamic Ob-Rb mRNA expression was higher (P<0·05) in females relative to males. Hypothalamic Ob-Rb protein showed a comparable developmental pattern (approximate threefold increase from fetal to postpubertal life), although a significant increase (15%; P<0·05) was observed between days 30 and 51 in females. Plasma leptin levels exhibited a dynamic pattern in both male and female rats during the prepubertal period, characterised by a precipitous fall after birth, relative stability to day 5, then a rapid increase to a transient peak on day 12. Plasma leptin then remained unchanged from day 15 in female rats but increased in males after puberty, thus confirming the well-recognised sex difference in adult rat leptin levels. In conclusion, this study shows that developmental increases occur not only in plasma leptin but also in hypothalamic Ob-Rb expression, suggesting that both are likely to influence the timing of puberty onset. Moreover, our data show that sex differences in both hypothalamic Ob-Rb and plasma leptin emerge only after puberty.

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“…Their studies showed that this surge did not depend on changes in fat mass or food intake, which suggests that it may be linked to an independent source of regulation not identified in their study. Similar findings in mice and rats were reported by Devaskar et al [82], who showed a rise in leptin levels as early as 2 postnatal days followed by a decline in leptin after postnatal day 14. Ahima et al [81] correlated this rise in leptin with a potential role for leptin as a neuroendocrine hormone and linked it to significant changes along the neuroendocrine axes.…”

supporting

confidence: 90%

Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

2011

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Leptin, a potent anorexigenic hormone secreted primarily by adipocytes, is known to be expressed in the anterior pituitary. Studies in our laboratory found leptin proteins and mRNA predominantly in somatotropes in normal male and cycling female rats. In contrast, leptin expression predominated in gonadotropes during pregnancy and lactation. Leptin expression varied with the cycle and was enhanced, in vitro by gonadotropin releasing hormone and Neuropeptide Y. In contrast, ghrelin inhibited pituitary leptin expression. Pituitary leptin in somatotropes or gonadotropes was reduced by nutritional deprivation for 24 h. However, growth hormone (GH), luteinizing hormone (LH) and pituitary leptin recovered if fasted animals were given glucose water. The glucose-mediated recovery suggests that the system is sensitive to changes in serum glucose. Somatotropes and gonadotropes also recovered if pituitary cells from fasted rats were stimulated in vitro with 1-100 pg/ml leptin. This in vitro leptin-mediated recovery suggests that leptin is important in the maintenance of somaotropes and gonadotropes. Collectively, the data suggest that pituitary leptin might serve as a "glucostat", sensing levels of serum glucose and reporting this nutritional state to somaotropes and gonadotropes in a paracrine manner. A decrease in pituitary leptin might signal nutritional deprivation to somatotropes and gonadotropes, lowering LH and GH production and allowing for conservation of resources. Lower GH would help conserve fat stores and lower LH would promote survival over reproduction.

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Developmental Changes inobGene Expression and Circulating Leptin Peptide Concentrations

Cited by 107 publications

References 25 publications

C/EBPα is required for differentiation of white, but not brown, adipose tissue

C/EBPα is required for differentiation of white, but not brown, adipose tissue

Developmental changes in plasma leptin and hypothalamic leptin receptor expression in the rat: peripubertal changes and the emergence of sex differences

Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

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