Low-calorie diet-induced weight loss is associated with altered brain connectivity and food desire in obesity

Abstract

Objective: The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in individuals with obesity.

Methods: A total of 25 individuals with obesity, among whom 9 had a diagnosis of type 2 diabetes, underwent functional magnetic resonance imaging (fMRI) scans before and after an 8-week low-calorie diet. We used a two-step hypereuglycemia clamp approach to mimic the changes in glucose levels observed in the postprandial period in combination with task-mediated fMRI intrinsic connectivity distribution (ICD) analysis.

Results: After the diet, participants lost an average of 3.3% body weight. Diet-induced weight loss led to a decrease in leptin levels, an increase in hunger and food intake, and greater brain connectivity in the parahippocampus, right hippocampus, and temporal cortex (limbic-temporal network). Group differences (with vs. without type 2 diabetes) were noted in several brain networks. Connectivity in the limbic-temporal and frontal-parietal brain clusters inversely correlated with hunger.

Conclusions: A short-term low-calorie diet led to a multifaceted body response in patients with obesity, with an increase in connectivity in the limbic-temporal network (emotion and memory) and hormone and eating behavior changes that may be important for recovering the weight lost.

Figure 1:

MRI with 2-Step Clamp Study Design Magnetic Resonance Imaging Visit: The visit consisted of a MRI scanning together with a two-step hyperglycemic-euglycemic clamp. fMRI was performed while participants were presented with a series of visual stimuli (food: high calorie (HC) and low calorie (LC), and non-food (NF) images). After viewing each image, participants provided liking and wanting ratings. Hunger was measured before and after each fMRI run. After the fMRI-clamp procedure, participants were provided an ad libitum buffet meal. This visit was performed twice: before and after an 8-week low calorie diet.

Figure 2:

Glucose and Hormone Levels during 2-Step Clamp Plasma glucose (Figure 2A), insulin (Figure 2B), glucose infusion rate (GIR) (Figure 2C), leptin (Figure 2D), ghrelin (Figure 2E), and GLP-1 (Figure 2F) levels during the 2-step (hyperglycemia-euglycemia) hyperinsulinemic clamp in OB(-T2D) (blue circle) and OB(+T2D) participants (red square) before (dashed lines) and after the diet (solid line). Data are presented as mean ± SD.

Figure 3:

Hunger and Food intake. Figure 3A depicts average hunger ratings during the MRI-clamp procedure before (dashed line) and after the diet (solid line). After each MRI scan, participants were offered a food buffet lunch meal in which the amounts of food consumed was measured and recorded. Figure 3B shows the total calories consumed of the buffet meal before and after the diet for all 25 study participants divided by amount of protein (prot), carbohydrate (carb), and fat (in kilocalories). Data are presented as mean ± SD. Significance at *P<0.05 and **P<0.001.

Figure 4:

Main Effect of Diet on Brain Connectivity Whole brain map of main effect of diet showing in red/yellow statistically significant connectivity in limbic network including right hippocampus and parahippocampus and BA22 (temporal cortex) and BA40 (parietal cortex) (initial threshold of P<0.001, whole brain, FWE corrected at P<0.05).

Figure 5:

Brain Connectivity Figure 5A: Group X Diet brain maps (Group: OB(-T2D) x OB(+T2D); Diet: Before x After) showing in red/yellow. Significantly increased connectivity was found comparing before and after diet in healthy OB(-T2D) (n = 16) than OB(-T2D) with T2D (n = 9) participants. Regions identified as significantly different showing in these brain slices were amygdala, hippocampus, hypothalamus, and anterior prefrontal cortex (PFC). Significance at P<0.05 initial threshold of P<0.001. Figure 5B depicts beta-values from ICD in hypothalamus-temporal lobe regions during hyperglycemia and euglycemia in OB(-T2D) (blue) and OB(+T2D) (red) groups before (pale bars) and after the diet (solid bars). Figures 5C and 5D: Correlations between hypothalamus-temporal lobes brain connectivity and average hunger during hyper and euglycemia before (r= 0.05, P=0.27) and after the diet (r=0.36, P<0.005).