High-fat feeding disrupts daily eating behavior rhythms in obesity-prone but not in obesity-resistant male inbred mouse strains

Abstract

Abnormal meal timing, like skipping breakfast and late-night snacking, is associated with obesity in humans. Disruption of daily eating rhythms also contributes to obesity in mice. When fed a high-fat diet, male C57BL/6J mice have disrupted eating behavior rhythms and they become obese. In contrast to obesity-prone C57BL/6J mice, some inbred strains of mice are resistant to high-fat diet-induced obesity. In this study, we sought to determine whether there are distinct effects of high-fat feeding on daily eating behavior rhythms in obesity-prone and obesity-resistant male mice. Male obesity-prone (C57BL/6J and 129X1/SvJ) and obesity-resistant (SWR/J and BALB/cJ) mice were fed low-fat diet or high-fat diet for 6 wk. Consistent with previous studies, obesity-prone male mice gained more weight and adiposity during high-fat diet feeding than obesity-resistant male mice. The amplitude of the daily rhythm of eating behavior was markedly attenuated in male obesity-prone mice fed high-fat diet, but not in obesity-resistant males. In contrast, high-fat feeding did not differentially affect locomotor activity rhythms in obesity-prone and obesity-resistant male mice. Together, these data suggest that regulation of the daily rhythm of eating may underlie the propensity to develop diet-induced obesity in male mice.

Keywords: circadian; eating behavior rhythm; high-fat diet; mouse; obesity.

Figure 1.

High-fat feeding causes obesity in obesity-prone, but not obesity-resistant, strains of male mice. Body weights were measured weekly from male C57BL/6J (A, n_LFD = 10; n_HFD = 20), 129X1/SvJ (D, n_LFD = 11; n_HFD = 11), SWR/J (G, n_LFD = 12; n_HFD = 12), and BALB/cJ (J, n_LFD = 11; n_HFD = 13) mice fed either low-fat diet (LFD) or high-fat diet (HFD) and analyzed with two-way repeated-measures ANOVA. All mice were fed LFD for 1 wk (7–8 wk old). HFD feeding began at 8 wk old in the HFD group. Percent fat mass (B, E, H, and K) and fasting blood glucose (C, F, I, and L) were measured in 14-wk-old C57BL/6J (B and C), 129X1/SvJ (E and F), SWR/J (H and I), and BALB/cJ (K and L) mice fed either LFD or HFD and were analyzed with Student’s t tests, except B, E, H, I, and K, which were analyzed with Mann–Whitney tests. Body weights (M, prone n_LFD = 21 LFD, n_HFD = 31; resistant n_LFD = 23, n_HFD = 25) were compared between male obesity-prone (C57BL/6J and 129X1/SvJ) and obesity-resistant (SWR/J and BALB/cJ) mice using three-way repeated-measures ANOVA with post hoc two-group t tests at each time point (Bonferroni-adjusted significance level = 0.006). Adiposity (N, prone n_LFD = 21; n_HFD = 31 HFD; resistant n_LFD = 22, n_HFD = 23) and fasting blood glucose (O, prone n_LFD = 21, n_HFD = 31; resistant n_LFD = 22, n_HFD = 22) were compared between male obesity-prone and obesity-resistant mice using two-way ANOVA. Data are means ± 95% confidence interval. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 2.

Food intake and activity do not differ between obesity-prone and obesity-resistant mice during high-fat feeding. Cumulative food intake was measured in male C57BL/6J (A, n_LFD = 10; n_HFD = 18), 129X1/SvJ (C, n_LFD = 11; n_HFD = 11), SWR/J (E, n_LFD = 12; n_HFD = 12), and BALB/cJ (G, n_LFD = 11; n_HFD = 13) mice fed either low-fat diet (LFD) or high-fat diet (HFD). Total locomotor activity counts were measured in male C57BL/6J (B, n_LFD = 10; n_HFD = 14), 129X1/SvJ (D, n_LFD = 8; n_HFD = 8), SWR/J (F, n_LFD = 7; n_HFD = 7), and BALB/cJ (H, n_LFD = 11; n_HFD = 12) mice. Locomotor activity counts could not be measured for some mice due to faulty infrared sensors. A–J were analyzed with Student’s t tests, except A, F, and H, which were analyzed with Mann–Whitney tests. Cumulative food intake (I, prone n_LFD = 21, n_HFD = 29; resistant n_LFD = 23, n_HFD = 25) and activity (J, prone n_LFD = 18; n_HFD = 22; resistant n_LFD = 18, n_HFD = 19) were compared between male obesity-prone (C57BL/6J and 129X1/SvJ) and obesity-resistant (SWR/J and BALB/cJ) mice using two-way ANOVA. Data are means ± 95% confidence interval. *P < 0.05, ***P < 0.001.

Figure 3.

High-fat feeding disrupts the eating behavior rhythm in obesity-prone, but not obesity-resistant, male mice. Representative circular histograms of eating behavior (10-min bins) during LFD (A, E, I, and M), short-term HFD (B, F, J, and N), and long-term HFD (C, G, K, and O) for C57BL/6J (A–C), 129X1/SvJ (E–G), SWR/J (I–K), and BALB/cJ (M–O) male mice (scale: inner circle, 0; middle circle, 5; outer circle, 10). Amplitudes (vector lengths) of the eating behavior rhythms of C57BL/6J (D, n = 8), 129X1/SvJ (H, n = 6), SWR/J (L, n = 7), and BALB/cJ (P, n = 7) male mice were analyzed with one-way repeated-measures ANOVA followed by Dunnett’s post hoc vs. LFD group. Q: eating behavior rhythm amplitudes were compared between obesity-prone (C57BL/6J and 129X1/SvJ; n = 14) and obesity-resistant mice (SWR/J and BALB/cJ; n = 14) using two-way repeated-measures ANOVA (time × group) and post hoc two-group t tests. Data are means ± 95% confidence interval. *P < 0.05, **P = 0.001.

Figure 4.

Locomotor activity rhythms do not differ between obesity-prone and obesity-resistant mice during high-fat feeding. Representative circular histograms of locomotor activity (10-min bins) during LFD (A, E, I, and M), short-term HFD (B, F, J, and N), and long-term HFD (C, G, K, and O) for C57BL/6J (A–C), 129X1/SvJ (E–G), SWR/J (I–K), and BALB/cJ (M–O) male mice (scale: inner circle, 0; middle circle, 30; outer circle, 60). Amplitudes (vector lengths) of the activity rhythms of C57BL/6J (D, n = 14), 129X1/SvJ (H, n = 8), SWR/J (L, n = 7), and BALB/cJ (P, n = 10) male mice were analyzed with one-way repeated-measures ANOVA followed by Dunnett’s post hoc vs. LFD group. Locomotor activity rhythm amplitudes (Q) and phases (R) were compared between obesity-prone (C57BL/6J and 129X1/SvJ; n = 22) and obesity-resistant mice (SWR/J and BALB/cJ; n = 17) using two-way repeated-measures ANOVA model (time × group). Data are means ± 95% confidence interval. *P < 0.05.

Figure 5.

Proposed model of circadian regulation of diet-induced obesity in different inbred strains of male mice. In obesity-prone strains of male mice (A), the amplitude of the daily rhythm of eating behavior is markedly decreased by high-fat diet (HFD) feeding. In contrast, in obesity-resistant strains of male mice (B), HFD feeding does not alter the amplitude of the daily eating behavior rhythm. The activity rhythm is not differentially affected by HFD feeding in obesity-prone or obesity-resistant male mice. In both obesity-prone and obesity-resistant male mice, HFD feeding increases food intake but does not alter activity levels. We propose that regulation of the eating behavior amplitude is a mechanism that regulates propensity or resistance to diet-induced obesity. ↑, ↓, and ↔ indicate increase, decrease, or no change, respectively, during HFD feeding compared with low-fat diet (LFD) feeding.