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Gene & Protein in Disease Genetic pleiotropy in birth weight and fat

and post-natal growth, thereby influencing birth weight. that PPARG expression is low in the placentas of small-
23
During childhood, IGF1R expression appears to be also for-gestational-age fetuses and is positively associated with
linked to the metabolic profile. Specifically, reduced fetal and placental weights within this subgroup. 57-59
expression of IGF1R in adipose tissue contributes to early On the other hand, PPARγ shows a relevant function in
adipose tissue dysfunction and a worsening metabolic adipocyte differentiation and a deregulation of PPARγ has
state in children with obesity. 46
been reported in obesity Screening patients with obesity
.
Concerning IGF2, as reported by Dunger et al., for PPARG expression indicated that levels of PPARγ
47
the common insulin (INS) variable nucleotide tandem increased in proportion to increased body mass index.
60
repeat (VNTR) mini-satellite, which regulates INS and Reduced activity or dysregulation of PPARγ signaling is
IGF2 expression, is been associated with size at birth. On associated with impaired adipocyte function and may
the other hand, they has been also linked to childhood contribute to the pathogenesis of obesity, 61,62 confirming its
48
obesity, predisposing to post-natal fat deposition, and to plausible role in control weight control.
metabolic comorbidities. 49
In addition, PPARγ is a key transcription factor
20
Osada also described a connection between IGF2 not only in adipocytes but also in macrophages, where
genetic polymorphisms and accelerated fetal growth, it modulates activation and inflammatory profiles.
supporting that IGF2 expression may play a role in the In obesity, macrophages infiltrate adipose tissue and
intrauterine programming of adipose tissue. In addition, contribute to a chronic low-grade inflammatory state,
50
IGF2 expression has been closely associated with weight promoting obesity-related complications. Activation of
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and adiposity in children, playing a key role in promoting PPARγ in macrophages promotes an anti-inflammatory
51
adipogenesis and fat storage. 52 (M2) phenotype, reducing the production of pro-
Furthermore, the methylation status of the IGF2 gene at inflammatory cytokines such as tumor necrosis factor-
birth has been linked to early childhood weight. St-Pierre alpha and interleukin 6. Therefore, in this context as well,
48
et al. showed that genetic and epigenetic variations at the expression and function of PPARs in macrophages
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the IGF2/H19 locus could be key factors influencing birth represent a significant factor in the pathophysiology
weight in a normal pediatric population. On the other hand, of childhood obesity and its associated metabolic
a significant link between the IGF2/H19 locus and obesity- complications. 63
related complications was also observed. Faienza et al. 3. Conclusion
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identified an association between the IGF2 polymorphism
(6815A/T) and hypertension in children and adolescents Given the dual role of the IGF-1/insulin axis, IGF-
with obesity; however, like other studies, they did not find 2, and PPARγ in fetal growth and adipogenesis, the
a direct association with obesity. potential involvement of a pleiotropic genetic effect in the

All this evidence highlights the role of IGF1, IGF2, relationship between birth weight and obesity warrants
and insulin as key determinants of both birth weight further consideration. Understanding the genetic interplay
and adiposity. In fact, while these factors predominantly between birth weight and adipose tissue regulation
regulate growth during fetal life, they play a significant offers valuable insights into the developmental origins of
role in controlling adipogenesis during infancy, childhood, childhood obesity. These findings highlight the critical
and adult age, influencing obesity risk and related importance of prioritizing both maternal and fetal health
comorbidities. during pregnancy. Future research should aim to integrate
genetic, epigenetic, and environmental factors to develop
Similarly to IGFs and insulin, PPARγ also plays a dual early, targeted interventions for high-risk populations,
role in fetal growth and adipocyte differentiation. 55-60 ultimately helping to alleviate the global obesity burden.
PPARs are members of the nuclear hormone receptor
subfamily, which comprises three distinct subtypes: Acknowledgments
PPARα, PPARβ/δ, and PPARγ. PPARγ is expressed None.
in various tissues and plays a central role in processes
such as adipogenesis, inflammatory response, and cell Funding
differentiation. During pregnancy, PPARγ influences
55
pre-term delivery and impaired fetal growth. 56,57 Exposure None.
to adverse events in early life can profoundly impact the Conflict of interest
methylation patterns of PPARs in the organs of offspring,
which may affect fetal development. Studies have reported The authors declare they have no competing interests.

Volume 4 Issue 3 (2025) 4 doi: 10.36922/GPD025070011