The possible regulations through cross-generation transmission on childhood obesity

Obesity and overweight are considered as one of the top health problem worldwide, obesity may induce both physical and mental health consequences [1, 2]. Obesity and overweight is regulated by both genetics and environmental factors which can control the balance between the lipid accumulation and energy expenditure, thus several bio-functional markers [3] of adipose tissues involve in the regulation of obesity, and obesity is also regulated by developmental age and nutrition [4]. Two interesting findings in the flied of lipid metabolism and obesity have been recently released on Pediatric Obesity by R. Somerville et al [5] and on Nature Medicine by Wenfei Sun et al [6]. Both studies focused on a very important topic in childhood obesity that is “How do a life course approach and living environment of previous generations affect lipid metabolism and obesity in the child?”. The work done by R. Somerville et al [5] showed that the central adiposity in grandmother, not grandfather, was positively consistent with that in children at the age of 5 and 9. However, cold exposure (CE) in the father, not mother, before conception may benefit for systemic metabolism as well as prevent overweight and obesity in the children as proved in the study done by Wenfei Sun et al [6]. In both humans and animals, CE increases the browning of white adipocytes and the thermogenesis of both brite (the brown adipocytes induced in white fat depots) and classical brown adipocytes, these effects lead to reduction in lipid accumulation and body fat, but increase in glucose and insulin sensitivity as well as systemic metabolism [7-12]. As results, CE was proved to reduce overweight and diet-induced obesity [10, 13].
The first report was conducted in a prospective cross-generational cohort of 1094 children (5 and 9 years old), 1082 mothers, and 745 grandparents of these children [5]. As waist circumference (WC) in one of indicator for determining obesity and overweight [14, 15], authors have performed mediation analysis on WC of study cohort and found a significant positive relationship of grandmother WC and grandchildren WC, but they did not see that correlation in WC between grandfather and grandchildren. This result indicates that cross-generation transmission maybe one of factors regulating childhood obesity (Fig. 1A).
The second report shows that environmental effects on father lead to changes in the systemic metabolism of offspring [6]. This has opened potential ways to control lipid metabolism and prevent obesity in human by optimizing ambient temperature at parents’ living places. It has been known that cold exposure activates the classical brown adipose tissue and induces functionally brite adipocytes in white fat depots in both human and animal models. The function of these thermogenic (brown and brite) adipocytes can improve the systemic metabolism and reduce fat mass [16-18, 12, 19], thus the cold exposure is considered as a potential therapy for controlling obesity and overweight [16, 18, 12]. In the current report [6], Wenfei Sun et al not only proved the anti-obesity effect of cold exposure but also went to a further step, because they showed that the browning effect of CE could transfer through from generations. Analyzing a cohort of 8,440 subjects, researchers found higher activities of thermogenic adipocytes in both brown (BAT) and white (WAT) fat tissues in children from the parents who were exposed to cold before impregnation or during pregnancy. Further investigations by authors showed that the CE effects on brown/brite adipocytes were only regulated through the paternal lineage.  These findings in humans were supported by the studies in mice, they found that higher thermogenesis and respiration were partially induced by an increase in BAT activation of pups from the fathers exposed to the cold, and the paternal CE (P-CE) could improve systemic metabolism and protected mouse offspring from diet induced obesity. Mechanically, investigators proved that the increase in BAT function of offspring maybe due to the changes in brown adipogenesis and neurogenesis induced by P-CE, and the elevated formation of thermogenic cells in offspring stimulated by P-CE was a cell autonomous manner.  Thus, the important findings by Wenfei Sun et al [6] suggest that CE in the father before conception may benefit for systemic metabolism as well as prevent overweight and obesity in the child (Fig. 1B).

The authors have no conflicts of interest to declare.