**2. The early-life origins of obesity**

Obesity is defined by an excess of adipose tissue and occurs when an imbalance in the balance of energy exists [14]. The origin of obesity is a complex process that involves genetic and environmental factors and is often associated with the development of chronic complications, such as hyperglycemia, hypertriglyceridemia, low HDL levels, and hypertension. Individuals who have at least three of these criteria are clinically diagnosed as having metabolic syndrome, which increases the risk of developing metabolic diseases, such as type 2 diabetes and cardiovascular diseases [15, 16].

In 2016, more than 1.9 billion adults, 18 years and older, were overweight. Of these, over 650 million were obese; 41 million children under the age of 5 were overweight or obese, as well as over 340 million children and adolescents aged 5–19 [14]. Recognizing its etiology is essential to face the global epidemic. This creates a challenge since the pathway to obesity in many individuals begins before birth; a predisposition to obesity can occur through epigenetic and other forms of early programming, and obesity and its metabolic consequences result from physiological changes set during fetal and early postnatal development [17–19].

It is known that a number of factors, including epigenetic signals, mitochondrial inheritance, milk composition, gut microbiota, and features of the maternal metabolic environment, such as insulin resistance, fatty acids, and inflammation, may cause developmental programming. In many cases, the effects of the prenatal perturbations are exacerbated by postnatal exposure to a high-calorie diet, accelerated postnatal growth, stress, or other factors [20–22].

The early-life origins of obesity are supported by a number of studies, which have shown that being exposed to inappropriately nutrition levels during critical periods of development (fetal and postnatal) is associated with increased risk of obesity, insulin resistance, and type 2 diabetes in child and adult life [23, 24]. The excessive or deficient nutritional status before birth alters the development of the fat cell, the adipocyte, and results in a permanent increase in the capacity to form new cells in adipose depots (adipogenesis) or to store lipid in existing adipocytes (lipogenesis) since the adipogenesis occurs primarily during late fetal and early postnatal life, and is highly sensitive to the nutritional environment at this time, in particular to the prevailing concentrations of insulin-like growth factors, glucose, insulin, and glucocorticoids [17, 25].

In addition, there are animal and human data that show that obese mothers are more likely to generate to an overweight baby and that these infants are at greater risk of obesity in later life. This "intergenerational cycle of obesity" already is a well-defined phenomenon, showing that maternal obesity, maternal diabetes, and an increase in nutrient supply to the developing fetus constitute major risk factors for obesity in postnatal life [26–28].

There is a greater propensity to develop altered energy metabolism in adult life, in particular, overweight and/or hyperphagia, after malnutrition during fetal development. This predisposition to develop obesity is particularly clear in the offspring of calorie-restricted dams and is also exacerbated when animals are exposed to an obesogenic environment in adulthood. Mechanisms contained in the deregulation of food intake and energy balance, due to perinatal nutrition, could be related to hypothalamic alterations and a lower capacity to respond to insulin and leptin signaling [29]. One potential mechanism of developmental programming is through permanent structural alterations of different organs. Different stress exposures (oxidative, immune, and inflammatory stresses, as well as maternal-placental-fetal endocrine disturbances) during the prenatal development could reprogram the telomere biology system [30, 31].
