Persistent Diet-Induced Obesity in Male C57BL/6 Mice Resulting from Temporary Obesigenic Diets

Abstract

BackgroundDoes diet-induced obesity persist after an obesigenic diet is removed? We investigated this question by providing male C57BL/6 mice with free access to two different obesigenic diets followed by a switch to chow to determine if obesity was reversible.Methodology/Principal FindingsMale C57BL/6 mice were randomly assigned to five weight-matched groups: 1) C group that continuously received a chow diet; 2) HF group on a 60% high fat diet; 3) EN group on the high fat diet plus liquid Ensure®; 4) HF-C group switched from high fat to chow after 7 weeks; 5) EN-C group switched from high fat plus Ensure® to chow after 7 weeks. All food intake was ad libitum. Body weight was increased after 7 weeks on both obesigenic diets (44.6±0.65, 39.8±0.63, and 28.6±0.63 g for EN, HF, and C groups, respectively) and resulted in elevated concentrations of serum insulin, glucose, and leptin and lower serum triglycerides. Development of obesity in HF and EN mice was caused by increased energy intake and a relative decrease of average energy output along with decreased ambulatory activity. After the switch to chow, the HF-C and EN-C groups lost weight but subsequently maintained a state of persistent obesity in comparison to the C group (34.8±1.2, 34.1±1.2 vs. 30.8±0.8 g respectively; P<0.05) with a 40–50% increase of body fat. All serum hormones and metabolites returned to control levels with the exception of a trend for increased leptin. The HF-C and EN-C groups had an average energy output in line with the C group and the persistent obesity was maintained despite a non-significant increase of energy intake of less than 1 kcal/d at the end of the study.ConclusionOur results illustrate the importance of considering the history of energy imbalance in determining body weight and that a persistent elevation of body weight after removal of obesigenic diets can result from very small increases of energy intake.

Obesity-programmed mice are rescued by early genetic intervention

“…This finding supports the conclusions drawn from both clinical (6, 7) and rodent models (11)(12)(13), which relied on high-fat dietinduced obesity, that a condition of chronic overweight leads to secondary adaptations in the central regulation of energy homeostasis that act to perpetuate obesity despite reductions in caloric intake. Furthermore, since we controlled for treatment, genetic, and environmental factors by rescuing central Pomc expression in inbred mouse siblings fed a standard chow of low hedonic value, our results show for the first time to our knowledge that obesity is a primary condition that permanently alters the normal body weight set point by imposing a maladaptive allostatic state that ultimately defends a greater body weight.…”

“…These problems worsen in extreme obesity (BMI >40 kg/m 2 ), a condition that is increasing alarmingly (9,10). Diet-induced obesity in rats and mice can also permanently elevate body weight set point after the animals are switched back to normal chow (11)(12)(13). However, unlike the allostatic changes in metabolism that occur during pregnancy or hibernation to promote "viability through change" (14), chronic overfeeding unrelated to physiological needs generates an allostatic state that slowly leads to obesity and is ultimately maladaptive to the health of an organism.…”

Diet-Induced Obesity Impairs the T Cell Memory Response to Influenza Virus Infection

“…Indeed, leptin is produced at high levels during inflammation and is involved in a number of immune pathways and cell types (45). As previously demonstrated (46,47), serum leptin levels are significantly elevated in DIO mice. In lean mice, leptin levels are significantly elevated postinfection; however, this response did not occur in the obese mice (Fig.…”

Size and phospholipid coating of lipid droplets in the diet of young mice modify body fat accumulation in adulthood

“…The results do not confirm whether the Concept IMF programs toward delayed ("slower") fat accumulation or rather toward a sustained reduced fat accumulation during aging. The WSD challenge was very mild as compared with obesogenic models using diets with 45-60% energy from fat (43,44) to model for mild obesogenic dietary patterns of many Western and developing countries. However, the WSD was even relatively moderate as compared with a diet resembling human Western dietary fat intake (45) and was therefore insufficient to sustain an adverse metabolic phenotype as compared with the nonchallenged reference group.…”