Intermittent energy restriction changes the regional homogeneity of the obese human brain

Abstract

Background: Intermittent energy restriction (IER) is an effective weight loss strategy. However, the accompanying changes in spontaneous neural activity are unclear, and the relationship among anthropometric measurements, biochemical indicators, and adipokines remains ambiguous.

Methods: Thirty-five obese adults were recruited and received a 2-month IER intervention. Data were collected from anthropometric measurements, blood samples, and resting-state functional magnetic resonance imaging at four time points. The regional homogeneity (ReHo) method was used to explore the effects of the IER intervention. The relationships between the ReHo values of altered brain regions and changes in anthropometric measurements, biochemical indicators, and adipokines (leptin and adiponectin) were analyzed.

Results: Results showed that IER significantly improved anthropometric measurements, biochemical indicators, and adipokine levels in the successful weight loss group. The IER intervention for weight loss was associated with a significant increase in ReHo in the bilateral lingual gyrus, left calcarine, and left postcentral gyrus and a significant decrease in the right middle temporal gyrus and right cerebellum (VIII). Follow-up analyses showed that the increase in ReHo values in the right LG had a significant positive correlation with a reduction in Three-factor Eating Questionnaire (TFEQ)-disinhibition and a significant negative correlation with an increase in TFEQ-cognitive control. Furthermore, the increase in ReHo values in the left calcarine had a significant positive correlation with the reduction in TFEQ-disinhibition. However, no significant difference in ReHo was observed in the failed weight loss group.

Conclusion: Our study provides objective evidence that the IER intervention reshaped the ReHo of some brain regions in obese individuals, accompanied with improved anthropometric measurements, biochemical indicators, and adipokines. These results illustrated that the IER intervention for weight loss may act by decreasing the motivational drive to eat, reducing reward responses to food cues, and repairing damaged food-related self-control processes. These findings enhance our understanding of the neurobiological basis of IER for weight loss in obesity.

Keywords: intermittent energy restriction; obesity; regional homogeneity; resting-state fMRI; weight loss.

Figure 1

Procedure of the IER intervention experiment. The average daily calorie intake of each participant was calculated based on a normal diet. Anthropometry measurements, blood samples, and resting-state fMRI data were collected before HCFP (day 4: baseline), at the midpoint of HCFP (day 20: MHCFP), at the endpoint of HCFP (day 36: EHCFP), and at the endpoint of LCFP (day 66: ELCFP). MHCFP, midpoint of the highly controlled fasting phase; EHCFP, endpoint of the highly controlled fasting phase; ELCFP, endpoint of the low-control fasting phase.

Figure 2

Effect of IER on anthropometry measurements. Repeated-measures ANOVA indicated that the IER intervention resulted in a significant reduction in all anthropometric measurements, including body weight (A), body mass index (B), waist circumference (C), body fat (D), percent of body fat (E), skeletal muscle (F), systolic blood pressure (G), and diastolic blood pressure (H), across the four time points. Data are expressed as the mean ± standard error of the mean. Abbreviations: endpoint of the highly controlled fasting phase, EHCFP; endpoint of the low-control fasting phase, ELCFP. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 3

Effect of intermittent energy restriction on blood biochemical indicators. Repeated-measures ANOVA indicated that the IER intervention resulted in significant changes in blood biochemical indicators, including fasting plasma glucose (A), glycosylated hemoglobin (B), total cholesterol (C), triglycerides (D), high-density lipoproteins (E), low-density lipoproteins (F), aspartate transaminase (G), alanine aminotransferase (H), glutamyl transpeptidase (I), alkaline phosphatase (J), serum creatinine (K), uric acid (L), leptin (M), and adiponectin (N) (except for serum creatinine), across the four time points. Data are expressed as the mean ± standard error of the mean. Abbreviations: midpoint of the highly controlled fasting phase, MHCFP; endpoint of the highly controlled fasting phase, EHCFP; endpoint of the low-control fasting phase, ELCFP. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 4

Effect of intermittent energy restriction on TFEQ. Repeated-measures ANOVA indicated that the IER intervention resulted in a significant reduction in TFEQ-disinhibition (A) and a significant increase in TFEQ-cognitive control (B) across the four time points, except for TFEQ-hunger (C). Data are expressed as the mean ± standard error of the mean. Abbreviations: Three-factor Eating Questionnaire, TFEQ; midpoint of the highly controlled fasting phase, MHCFP; endpoint of the highly controlled fasting phase, EHCFP; endpoint of the low-control fasting phase, ELCFP. **p < 0.01 and ***p < 0.001.

Figure 5

Brain regions exhibited changed ReHo in individuals with obesity induced by intermittent energy restriction intervention (A). Repeated-measures ANOVA indicated that the IER intervention resulted in a significant increase in ReHo in the bilateral lingual gyrus (B,D), left calcarine (C), and left postcentral gyrus (E) and a significant decrease in the right middle temporal gyrus (F) and right cerebellum (VIII) (G). Data are expressed as the mean ± standard error of the mean. Abbreviations: regional homogeneity, ReHo; midpoint of the highly controlled fasting phase, MHCFP; endpoint of the highly controlled fasting phase, EHCFP; endpoint of the low-control fasting phase, ELCFP; L, left; R, right. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 6

Scatter plots showing the relationship between changes in leptin/adipokines and changes in body weight (A), body mass index (B), body fat (C), and skeletal muscle (D) for the comparison of ELCFP with the baseline during IER. Abbreviation: endpoint of the low-control fasting phase, ELCFP.

Figure 7

Scatter plots showing the relationship between changes in TFEQ and changes in body weight (A), body mass index (B), skeletal muscle (C), systolic blood pressure (D), triglyceride (H) and ReHo values in altered brain regions [left calcarine (E) and right lingual gyrus (F,G)] for the comparison of ELCFP with the baseline during IER. Abbreviations: regional homogeneity, ReHo; Three-factor Eating Questionnaire, TFEQ; endpoint of the low-control fasting phase, ELCFP.