Developmental influences on circuits programming susceptibility to obesity

Zeltser, Lori M.

doi:10.1016/j.yfrne.2015.07.002

Cited by 30 publications

(37 citation statements)

References 163 publications

(287 reference statements)

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“…These data are consistent with numerous studies showing that maternal exposure to environmental stressors exerts long-term energy metabolic effects on offspring through programming of hypothalamic circuits regulating energy balance [21]. Further studies are undergoing to identify the structural and/or functional alterations in the hypothalamus that may account for the decreased expression of NPY and food intake.…”

Section: Discussionsupporting

confidence: 89%

Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism

et al. 2017

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BackgroundObesity is one of the leading threats to global public health. It is consequent to abnormal energy metabolism. Currently, it has been well established that maternal exposure to environmental stressors that cause inappropriate fetal development may have long-term adverse effects on offspring energy metabolism in an exposure timing-dependent manner, known as developmental programming of health and diseases paradigm. Rapidly increasing evidence has indicated that maternal exposure to ambient fine particles (PM2.5) correlates to abnormal fetal development. In the present study, we therefore assessed whether maternal exposure to diesel exhaust PM2.5 (DEP), the major component of ambient PM2.5 in urban areas, programs offspring energy metabolism, and further examined how the timing of exposure impacts this programming.ResultsThe growth trajectory of offspring shows that although prenatal maternal exposure to DEP did not impact the birth weight of offspring, it significantly decreased offspring body weight from postnatal week 2 until the end of observation. This weight loss effect of prenatal maternal exposure to DEP coincided with decreased food intake but not alteration in brown adipose tissue (BAT) morphology. The hypophagic effect of prenatal maternal exposure to DEP was in concord with decreased hypothalamic expression of an orexigenic peptide NPY, suggesting that the prenatal maternal exposure to DEP impacts offspring energy balance primarily through programming of food intake. Paradoxically, the reduced body weight resulted from prenatal maternal exposure to DEP was accompanied by increased mass of epididymal adipose tissue, which was due to hyperplasia as morphological analysis did not observe any hypertrophy. In direct contrast, the postnatal mothering by DEP-exposed dams increased offspring body weight during lactation and adulthood, paralleled by markedly increased fat accumulation and decreased UCP1 expression in BAT but not alteration in food intake. The weight gain induced by postnatal mothering by DEP-exposed dams was also expressed as an increased adiposity. But it concurred with a marked hypertrophy of adipocytes.ConclusionPrenatal and postnatal mothering by DEP-exposed dams differentially program offspring energy metabolism, underscoring consideration of the exposure timing when examining the adverse effects of maternal exposure to ambient PM2.5.

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Section: Discussionsupporting

confidence: 89%

Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism

et al. 2017

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“…In some cases it has been shown that genes involved in the thermoregulatory response are direct targets of circadian clock transcription factors 32 . The current analysis indicates that the light-OPN3 pathway is required for development of the thermosensory response 28 . We have shown the light-OPN3 pathway regulates Leptin , an adipokine implicated in this aspect of development.…”

mentioning

confidence: 72%

“…Furthermore, Opn3 null mice show low “brite” adipocyte content in inWAT and abnormal mitochondrial morphology in iAT. In neonatal mice, Leptin , found at low levels in Opn3 null mice, is required for establishing the thermogenesis circuit 28 . The TRP channels that cluster in transcriptome analysis of the Opn3 null, function as thermosensors 29 .…”

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confidence: 99%

An adipocyte light-Opsin 3 pathway regulates the circadian clock and energy balance

Vemaraju

Nayak

Buhr

et al. 2018

Preprint

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Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, where photoreceptor signals are processed into virtual images, and the circadian system, where light entrains a physiological clock. Here we describe a pathway in mice that employs encephalopsin (OPN3, a 480 nm light responsive opsin) to mediate light responses in murine adipocytes. The adipocyte light-OPN3 pathway regulates neonatal growth in mice and is required for at least three important functions including (1) photoentrainment of a local circadian clock, (2) extracellular matrix deposition, and (3) regulation of mitochondrial content and the proportion of “brite” adipocytes. Furthermore, we show that the light-OPN3 pathway is required for normal levels of uncoupling protein 1 (UCP1) in white and brown adipose tissue. Consequently, neonatal Opn3 germ-line and adipocyte-conditional null mice show a reduced ability to maintain their body temperature under cold stress. This was also observed in wild-type mice deprived of blue light. We hypothesize that the adipocyte light-OPN3 pathway provides a dynamically responsive, circadian clock-integrated mechanism for regulating adipocyte function and in turn directing metabolism to thermogenesis rather than anabolism. These data indicate an important role for peripheral light sensing in mammals and may have broad implications for human health given the unnatural lighting conditions in which we live.

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“…The impact of fetal adipocytokines on growth and obesity risk during childhood is unclear. Evidence from animal studies has suggested that fetal leptin and adiponectin exposure induces changes in hypothalamic circuits and adipose tissue deposition, respectively, which may in turn increase offspring adiposity . Fewer studies have quantified the association between fetal adipocytokines and growth (i.e., change in anthropometry over time), and the results have been inconclusive .…”

Section: Introductionmentioning

confidence: 99%

Neonatal Adipocytokines and Longitudinal Patterns of Childhood Growth

Buck

Eliot

Kelsey

et al. 2019

Obesity

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Objective Adipocytokines are markers of fetal metabolism, but their association with childhood growth is unclear. This study examined associations of neonatal adipocytokines with longitudinal childhood adiposity measures in a prospective cohort of pregnant women and their children. Methods We measured leptin and adiponectin concentrations at delivery and children’s body mass index (BMI) z-scores between ages 4 weeks and 8 years. We estimated differences in BMI z-scores and rates of BMI z-score change by leptin (N = 257) and adiponectin (N = 271) terciles. Results Children in the middle (mean difference: 0.2; 95% CI: −0.1, 0.4) and highest (0.4; 95% CI: 0.1, 0.6) leptin terciles had greater BMI z-scores than children in the lowest tercile. Associations were null after adjustment for birthweight z-score. Children in the lowest adiponectin tercile had greater gains in BMI z-score (change per year: 0.10; 95% CI: 0.08, 0.13) than children in the middle (0.07; 95% CI: 0.04, 0.09) and highest terciles (0.04; 95% CI: −0.01, 0.05) (adiponectin x age interaction P < 0.001). Conclusions Lower adiponectin levels were associated with increased rates of BMI gains in the first 8 years of life. While leptin was positively associated with BMI, this association may be confounded by birthweight.

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Developmental influences on circuits programming susceptibility to obesity

Cited by 30 publications

References 163 publications

Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism

Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism

An adipocyte light-Opsin 3 pathway regulates the circadian clock and energy balance

Neonatal Adipocytokines and Longitudinal Patterns of Childhood Growth

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