Related Experiment Video

Updated: Feb 6, 2026

Protein Modifications: Protein Kinases and Phosphatases
02:54

Protein Modifications: Protein Kinases and Phosphatases

15.2K

Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice

Jaemin Lee1, Junli Liu1, Xudong Feng1

  • 1Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Nature Medicine
|August 2, 2016
PubMed

Insights

Withaferin A, a natural compound, effectively reduces body weight and improves metabolic health in obese mice by increasing leptin sensitivity. This offers a promising new therapeutic strategy for obesity and related disorders.

Area of Science:

  • Metabolic disease research
  • Pharmacology
  • Obesity therapeutics

Background:

  • Global obesity rates are rising, necessitating new weight loss treatments.
  • Obesity involves high leptin levels and resistance to its effects.
  • Celastrol was previously identified as a leptin sensitizer.

Purpose of the Study:

  • To find compounds that reverse leptin resistance and promote weight loss.
  • To investigate withaferin A as a potential leptin sensitizer.

Main Methods:

  • Screened small molecules with expression profiles similar to celastrol.
  • Treated diet-induced obese (DIO) mice with withaferin A.
  • Assessed body weight, hepatic steatosis, and glucose metabolism.

Main Results:

  • Withaferin A treatment reduced body weight by 20-25% in DIO mice.
  • It improved obesity-associated abnormalities like hepatic steatosis.
  • Withaferin A demonstrated beneficial effects on glucose metabolism independent of leptin sensitization.

Conclusions:

  • Withaferin A is a potent leptin sensitizer with therapeutic potential for obesity.
  • It offers additional benefits for glucose metabolism, suggesting broader antidiabetic applications.

More Related Videos

Regulated and Targeted Protein Degradation02:58

Regulated and Targeted Protein Degradation

8.9K
Covalently Linked Protein Regulators and Post-translational Modification02:04

Covalently Linked Protein Regulators and Post-translational Modification

9.6K

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.2K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.6K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.7K
Activation Energy01:26

Activation Energy

Activation energy is the minimum amount of energy necessary for a chemical reaction to move forward. The higher the activation energy, the slower the rate of the reaction. However, adding heat to the reaction will increase the rate, since it causes molecules to move faster and increase the likelihood that molecules will collide. The collision and breaking of bonds represents the uphill phase of a reaction and generates the transition state. The transition state is an unstable high-energy state...
86.7K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
11.5K