Natural and Artificial Sweeteners and High Fat Diet Modify Differential Taste Receptors, Insulin, and TLR4-Mediated Inflammatory Pathways in Adipose Tissues of Rats

Nutrients. 2019 Apr 19;11(4):880. doi: 10.3390/nu11040880.


It is difficult to know if the cause for obesity is the type of sweetener, high fat (HF) content, or the combination of sweetener and fat. The purpose of the present work was to study different types of sweeteners; in particular, steviol glycosides (SG), glucose, fructose, sucrose, brown sugar, honey, SG + sucrose (SV), and sucralose on the functionality of the adipocyte. Male Wistar rats were fed for four months with different sweeteners or sweetener with HF added. Taste receptors T1R2 and T1R3 were differentially expressed in the tongue and intestine by sweeteners and HF. The combination of fat and sweetener showed an additive effect on circulating levels of GIP and GLP-1 except for honey, SG, and brown sugar. In adipose tissue, sucrose and sucralose stimulated TLR4, and c-Jun N-terminal (JNK). The combination of HF with sweeteners increased NFκB, with the exception of SG and honey. Honey kept the insulin signaling pathway active and the smallest adipocytes in white (WAT) and brown (BAT) adipose tissue and the highest expression of adiponectin, PPARγ, and UCP-1 in BAT. The addition of HF reduced mitochondrial branched-chain amino transferase (BCAT2) branched-chain keto acid dehydrogenase E1 (BCKDH) and increased branched chain amino acids (BCAA) levels by sucrose and sucralose. Our data suggests that the consumption of particular honey maintained functional adipocytes despite the consumption of a HF diet.

Keywords: BCAA; TLR4; adipose tissue; incretins; insulin signaling; sweeteners; taste receptors.

MeSH terms

  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / blood
  • Adiponectin / blood
  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects*
  • Animals
  • Diet, High-Fat*
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology
  • Dietary Sugars / pharmacology*
  • Honey
  • Incretins / blood
  • Inflammation / metabolism
  • Insulin / blood*
  • Male
  • Membrane Transport Proteins / blood
  • Mitochondrial Proteins
  • Monocarboxylic Acid Transporters
  • NF-kappa B / metabolism
  • Obesity / etiology
  • Obesity / metabolism
  • PPAR gamma / blood
  • Rats, Wistar
  • Solute Carrier Proteins
  • Stevia
  • Sucrose / analogs & derivatives
  • Sucrose / pharmacology
  • Sweetening Agents / pharmacology*
  • Taste
  • Taste Buds / metabolism*
  • Toll-Like Receptor 4 / metabolism*
  • Transaminases
  • Uncoupling Protein 1 / blood


  • Adiponectin
  • Dietary Fats
  • Dietary Sugars
  • Incretins
  • Insulin
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Monocarboxylic Acid Transporters
  • Mpc1 protein, rat
  • NF-kappa B
  • PPAR gamma
  • Solute Carrier Proteins
  • Sweetening Agents
  • Toll-Like Receptor 4
  • Ucp1 protein, rat
  • Uncoupling Protein 1
  • Sucrose
  • trichlorosucrose
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
  • Transaminases
  • Bcat2 protein, rat