Different brain responses to fat and/or sugar

Sugar and fat intake are considered to be ‘bad guys’, as they increase the risk to develop obesity, cardiovascular diseases, and type 2 diabetes. Although both obesogenic, sugar and fat differ in the way they influence the underlying processes in the brain.

Recent findings – predominantly based on results from animal studies – on how sugar and fat interact with the brain were reviewed by Prof. Susanne la Fleur (University of Amsterdam, the Netherlands) [1]. Using experimental free-choice diet conditions, where rats are fed with different types of chow (normal, high-fat [HF], high-sugar [HS], high-fat and high-sugar [HFHS]), Prof. la Fleur showed that both HF and HFHS diets initially increased caloric intake. However, after 4 weeks, caloric intake only continued to be elevated in animals on a HFHS diet and was not adjusted to becoming obese. In contrast, animals on a HS diet normalised their caloric intake, although shifting to an unhealthier (i.e. more sugar-containing) diet [2]. Animals on a HFHS diet, in contrast to animals on a HF or HS diet, were also highly motivated to work for a sugar reward [3].

More recent experiments showed that giving animals only a sugar bolus in the morning increased fat intake during the rest of the day. The observed effect could be mimicked by infusion of the µ-opioid receptor agonist DAMGO ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin) into the nucleus accumbens of the animals [4], indicating that the nucleus accumbens plays a role in the central effects of opioids on glucose metabolism. This highlights the possibility of using nucleus accumbens μ-opioid receptors as a therapeutic target to enhance the counter-regulatory response, according to Prof. la Fleur.

In addition, it has been shown that glutamatergic lateral hypothalamus (LH) neurons are capable of discriminating sucrose from water and sucralose, a low-calory sweetener. While water and sucralose activate the LH^glut receptors (and decrease dopamine output), sucrose does not. However, consumption of a HF diet does disrupt this calorie detection and LH activation. In animals on a HF diet, both water and sucrose activated the LH^glut receptors, while sucralose did not (anymore) and probably is rewarding by increasing the dopamine output [5].

1. La Fleur SE, et al. How junk food affects reward brain regions and drives hyperphagia. Abstract S01.03, ECNP Congress 2022, 15–18 October, Vienna, Austria.
2. La Fleur SE, et al. Int J Obes (Lond). 2011;35:595–604.
3. Slomp M, et al. J Neuroendocrinol. 2019;31:e12718.
4. Koekkoek LL, et al. J Neuroendocrinol. 2021;33:e13036.
5. Koekkoek LL, et al. FASEB Journal. 2021;35:e21804.

 

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Posted on 28 November, 2022