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Different brain responses to fat and/or sugar

Presented by
Prof. Susanne la Fleur, University of Amsterdam, the Netherlands
ECNP 2022
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 LHglut 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 LHglut 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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