Differential effects of high-fat diet on glucose tolerance, food intake, and glucocorticoid regulation in male C57BL/6J and BALB/cJ mice

Dec 15, 2019Physiology & behavior

High-fat diet's different impacts on blood sugar control, eating, and stress hormone regulation in two male mouse strains

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Abstract

C57BL/6J mice showed significantly impaired glucose tolerance compared to BALB/cJ mice when both were subjected to a low-fat diet.

Young adult BALB/cJ mice exhibited much lower weight gain and metabolic effects from a high-fat diet compared to C57BL/6J mice.
Feeding behavior in C57BL/6J mice on a high-fat diet increased during the daytime, leading to impaired glucose regulation.
Restricting food availability to nighttime prevented significant increases in fat mass in C57BL/6J mice, despite overall weight gain.
Both mouse strains demonstrated blunted baseline corticosterone levels after 8 weeks on a high-fat diet, without changes in baseline glucose levels.
C57BL/6J mice experienced exaggerated stress-induced increases in corticosterone and blood glucose, while BALB/cJ mice showed exaggerated corticosterone responses with blunted glucose responses.

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The C57BL/6J strain of laboratory mice is a popular subject for studies of diet-induced obesity and diabetes given its propensity for developing obesity and glucose intolerance when placed on high-fat diet. High-fat diet leads to much lower weight gain in young adult BALB/cJ mice, which appear to be protected from many of the metabolic effects of high-fat diet observed in C57BL/6J mice. In this report, the effects of diet and timing of feeding on body weight, food intake, glucose tolerance, and stress-induced corticosterone and blood glucose responses were assessed in male C57BL/6J and BALB/cJ mice. Lower glucose tolerance was observed in low-fat diet-fed C57BL/6J than BALB/cJ mice at four times sampled across the circadian cycle. Ad libitum high-fat diet increased the amount of daytime eating behavior and led to impaired glucose regulation in C57BL/6J but not BALB/cJ mice. Restricting food availability to either daytime or nighttime did not prevent overall body weight gain, but restricting feeding to nighttime (but not daytime) did prevent the significant increase in perigonadal fat pad mass produced by high-fat diet in C57BL/6J mice. Baseline corticosterone levels at their typical daily peak near onset of daily activity were blunted in both strains of mice after 8 weeks on high-fat diet, without corresponding differences in baseline glucose levels. Restraint stress-induced increases in corticosterone were exaggerated in C57BL/6J mice on high-fat diet, with concomitant increases in blood glucose. Paradoxically, stress-induced corticosterone responses were even more exaggerated in BALB/cJ mice yet with significantly blunted glucose responses compared to C57BL/6J mice, regardless of diet, indicating that corticosterone does not have equivalent glucogenic effects in young adult male BALB/cJ and C57BL/6J mice on high-fat diet. These results document considerable strain differences that may provide means for elucidating the mechanisms involved in diet-induced obesity, while highlighting the need to consider these strain differences when extending the results of mouse studies toward the human condition.

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Differential effects of high-fat diet on glucose tolerance, food intake, and glucocorticoid regulation in male C57BL/6J and BALB/cJ mice

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