Evaluation of anti-obesogenic and anti-diabetic effects of tauroursodeoxycholic acid in Swiss albino rats: possible blockage of CHOP-dependent mitochondrial shuttling of TBP-2 and antagonism of streptozotocin-induced type 2 diabetes

Aitijjo Bhowmick; Khokon Dutta; Ratan Hossain; Esita  Halder; Probir Banjerjee; Tofazzal Hossain; Muslima Khatun; Nigar Sultana; Manoj Mandal

doi:10.71193/jcid.20250009

Authors

Aitijjo Bhowmick Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0005-9633-8536
Khokon Dutta Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0003-2453-1279
Ratan Hossain Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0003-1193-3957
Esita Halder Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0007-0453-6733
Probir Banjerjee Department of Gastroenterology, Gopalganj Medical College & Hospital, Goplaganj 8100, Bangladesh Author https://orcid.org/0009-0002-6692-4444
Tofazzal Hossain Department of Statistics, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0000-0002-8281-6059
Muslima Khatun Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0004-1801-1928
Nigar Sultana Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0000-9572-923X
Manoj Mandal Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0001-1431-8250

DOI:

https://doi.org/10.71193/jcid.20250009

Keywords:

Bile acids, blockage mitochondrial shuttling, obesity, streptozotocin antagonism, type 2 diabetes

Abstract

Endoplasmic reticulum (ER) stress plays a critical role in the progression of type 2 diabetes mellitus (T2DM) through activation of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP). Accumulation of CHOP in the nucleus promotes thioredoxin-interacting protein (TXNIP) expression and its translocation to mitochondria, thereby contributing to mitochondrial dysfunction and β-cell loss. Tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) are established inhibitors of ER stress–induced CHOP expression. This study evaluated the combined effects of TUDCA and UDCA on body weight regulation and glycemic control in a rat model of T2DM induced by high-fat diet (HFD) feeding and low-dose streptozotocin (STZ). Swiss albino male rats were divided into four groups: control, HFD control, diabetic (HFD+STZ), and treatment [HFD+STZ+TUDCA (0.02%)/UDCA (0.3%)]. Body weight, fasting blood glucose, and postprandial blood glucose were assessed over 90 days. Supplementation with TUDCA and UDCA significantly reduced weight gain and improved glycemic control in diabetic rats (p < 0.0001). The incidence of diabetes was substantially lower in the treatment group compared with untreated diabetic rats, with 0% vs. 50% incidence by day 54 and 34% vs. 75% by day 90. By day 90, PBG levels were significantly lower in treated diabetic rats than in untreated diabetic rats (p < 0.0001). These findings indicate that combined TUDCA and UDCA supplementation exerts strong anti-obesogenic and anti-diabetic effects, enhancing glucose homeostasis and delaying diabetes onset. These findings suggest that blockers of TBP-2 mitochondrial shuttling, such as TUDCA and UDCA, may represent promising strategies for the prevention and treatment of T2DM.

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