Peripubertal-onset but not adult-onset obesity increases IGF-I and drives development of lean mass, which may lessen the metabolic impairment in adult obesity

Abstract

It has been suggested that adult metabolic dysfunction may be more severe in individuals who become obese as children compared with those who become obese later in life. To determine whether adult metabolic function differs if diet-induced weight gain occurs during the peripubertal age vs. if excess weight gain occurs after puberty, male C57Bl/6J mice were fed a low-fat (LF; 10% kcal from fat) or high-fat (HF; 60% kcal from fat) diet starting during the peripubertal period (pHF; 4 wk of age) or as adults (aHF; 12 wk of age). Both pHF and aHF mice were hyperinsulinemic and hyperglycemic, and both showed impaired glucose tolerance and insulin resistance compared with their LF-fed controls. However, despite a longer time on diet, pHF mice were relatively more insulin sensitive than aHF mice, which was associated with higher lean mass and circulating IGF-I levels. In addition, HF feeding had an overall stimulatory effect on circulating corticosterone levels; however, this rise was associated only with elevated plasma ACTH in the aHF mice. Despite the belief that adult metabolic dysfunction may be more severe in individuals who become obese as children, data generated using a diet-induced obese mouse model suggest that adult metabolic dysfunction associated with peripubertal onset of obesity is not worse than that associated with adult-onset obesity.

PICK1 Deficiency Impairs Secretory Vesicle Biogenesis and Leads to Growth Retardation and Decreased Glucose Tolerance

“…We also measured plasma IGF-1 levels in the DIO mice as a marker of GH secretion and found a trend toward an increase. Interestingly, a significant increase in circulating IGF-1 levels was found in a recent study on obese mice introduced to a high-fat diet at a slightly younger age than the mice used on our study [54]. Furthermore, it should be noted that evaluation of the plasma level of free or total IGF-1 in obesity might be complicated by factors such as IGF binding proteins and fat mass [55].…”

Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I

“…High-fat-fed IGF-I-deficient mice showed no difference from control mice in glucose tolerance tests (38,003 vs. 37,640 integrated AUC, P ϭ 0.92), suggesting that their relative impairment due to high-fat feeding was not to the same degree as that of control mice. IGF-I-deficient mice still differed from control mice in their response to insulin tolerance tests (12,152 vs. 15,429 integrated AUC, P ϭ 0.002); however, it is interesting to note that high-fat-fed control mice were severely glucose intolerant and insulin resistant compared with their chow-fed controls, whereas chow-fed and high-fat-fed IGF-I-deficient mice differed minimally in these tests (Figs. 1 and 4).…”

“…Conversely, mice that express elevated levels of IGF-I preserve insulin sensitivity when fed a high-fat diet, although they are not protected from fat accumulation (40,41). There is also evidence that the relationship between obesity and IGF-I levels appears to be stronger in young mice and reduced in mice with adult-onset obesity (12). IGF-I signaling has been shown to play a major role in the regulation of age-related diseases, including alterations in metabolic function that may promote obesity (49).…”

Maternal Obesity Has Little Effect on the Immediate Offspring but Impacts on the Next Generation

“…Experiments have differed in terms of species (rat and mouse) and strain of animal used and the length of time females were exposed to the diet before mating. This is likely to be important in determining the extent of maternal metabolic dysfunction and thus offspring outcome (32). Importantly, the types of diet used and the dietary constituents have differed between studies; some have used diets only high in fat content (with the type of fat differing between studies), or high-fat combined with high-sugar cafeteria diets (9).…”