Causes and consequences of obesity: the contribution of recent twin studies

Abstract

Obesity is a genetically complex disorder that produces a myriad of health problems. Most of the recognized complications of obesity are not only strongly influenced by lifestyle factors, but also present with independent genetic predispositions that are notoriously difficult to disentangle in humans. Most studies on the causes and consequences of acquired obesity are encumbered by the incomplete ability to control for genetic influences. However, utilizing a unique experiment of nature, namely monozygotic twins (MZ) discordant for obesity as 'clonal controls' of obese and non-obese individuals has enabled the fine characterization of the effects and possible antecedents of acquired obesity while controlling for the genetic background, as well as pointed to novel obesity predisposing candidate genes. This review is a distillation of the findings from more than 10 years of research done in an exceptionally well-characterized collection of MZ and dizygotic (DZ) twins, based on the Finnish Twin Cohorts. Topics covered include the nature of development of obesity from the childhood onwards, the role of exercise in modifying the genetic susceptibility, the resulting inflammatory, prediabetic and preatherosclerotic changes in whole body and adipose tissue physiology, as well as the newest insights provided by the omics revolution. Keywords: adipose tissue; inflammation; liver fat; insulin resistance; BMI; metabolic syndrome INTRODUCTION Across time people have been fascinated by monozygotic (MZ) twins and their striking similarities in appearance, behavior as well as aspects of health and disease. In mythology, twins are often described as two halves of a whole, or alternatively as polar opposite representations of good and evil. MZ twins result from the early splitting of a single zygote and thereby are identical at the level of DNA sequence (precluding somatic mutations, epigenetic modifications and other genetic changes), whereas dizygotic (DZ) twins result from two different ova being fertilized by two separate sperm and share on average 50% of their segregating genes---just as ordinary siblings in a family. Most of the early genetic research into the heritability and variance of human traits was based on measuring the differences in within-pair correlations of various phenotypic traits between pairs of MZ and DZ twins. In addition to complex, continuous phenotypes such as height, weight and aspects of personality where MZ twins exhibit a high degree of similarity, MZ twins are nearly always concordant for Mendelian genetic diseases. Studying cases where MZ twins present with differences in the manifestation (onset, severity, response to treatment, and so on) of Mendelian diseases has helped to uncover disease mutations as well as broadened the clinical spectrum of diseases previously thought to be more uniform in presentation (Reviewed by Zwijnenburg et al., 2010). 1 Recently discordant MZ twins have also been utilized in the hunt for polymorphisms contributing to complex traits such as obesity. 2 Twin studies ha...

Habitual Dietary Intake Is Associated with Stool Microbiota Composition in Monozygotic Twins

“…The participants were divided in categories according to their BMI (in kg/m 2 ) as follows: normal weight (19 # BMI < 25), overweight (25 # BMI < 30), and obese (BMI $ 30) ( Table 1). Nine twin pairs were concordant (BMI difference <3 kg/m 2 ) and 11 pairs were discordant for BMI (BMI difference $3 kg/m 2 ); a BMI difference of 3 kg/m 2 represented the top 5% most discordant MZ twin pairs (25,27). Eleven of the twin pairs were female and 9 were male.…”

Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults

“…Studies in older adults also identified the BCAA-related signature, and reported higher leucine/ isoleucine and valine in obese compared with nonobese individuals (4,(9)(10)(11). Furthermore, experimental research using metabolomic profiling identified causal effects of weight gain on multiple blood metabolites, including elevation of BCAAs, very low-density lipoprotein (8,10,12), triacylglycerol (10), C-reactive protein (8,10), and insulin-like growth factor (10).…”

“…About 75% of the population experiences weight gain during this transition (2, 3), but there have been few efforts to identify biomarkers of risk that could guide prevention efforts. A study (4) in monozygotic twins discordant for body mass index (BMI) reported divergence at about the age of 18 y, corresponding to a time in life when the environment shifts, and further underscoring the importance of young adulthood in the lifetime trajectory of adiposity and as a window of opportunity for prevention (5).…”

Ten-Year obesity and overweight prevalence in Greek children: A systematic review and meta-analysis of 2001-2010 data

“…The independent genetic predispositions associated with OB are difficult to disentangle in humans. 62 Additionally, OB treatment is mainly based on behavioral approaches. Thus, we are in need of evidence on the environmental aspects of the condition in order to be able to design interventions.…”