A Novel Glucomannan from <i>Dendrobium officinale</i> Inhibits Obesity and Improves Insulin Sensitivity through Regulating Adipogenesis and Lipid Metabolism

<i>Dendrobium officinale</i> polysaccharides (DOPs), the main active components of <i>D. officinale</i>, exhibit diverse pharmacological activities. Although crude DOPs exhibit antiobesity potential, research investigating purified DOPs remains limited. This study purified a bioactive polysaccharide (DOP-1) from <i>D. officinale</i> and revealed that DOP-1 is a homogeneous glucomannan with a molecular weight (<i>M</i>_w) of 1.09 × 10⁵ Da. The primary backbone of DOP-1 is composed of →4)-α-d-Glc<i>p</i>-(1→, →4,6)-α-d-Glc<i>p</i>-(1→, →4)-β-d-Man<i>p</i>-(1→, and →4)-β-d-2-OAc-Man<i>p</i>-(1→ units, while the side chain features α-d-Glc<i>p</i>-(1→ residues. Animal studies revealed that DOP-1 prevents high-fat diet (HFD)-induced obesity by mitigating weight gain, reducing inflammation, improving glucose and lipid metabolism, and alleviating insulin resistance (IR). Additionally, DOP-1 inhibited 3T3-L1 preadipocyte differentiation and lipid accumulation. Concurrently, DOP-1 enhanced lipolysis, fatty acid oxidation, and browning, ultimately enhancing insulin sensitivity in mature adipocytes. Furthermore, DOP-1 showed similar effects in HFD-fed mice. These findings suggest that DOP-1 holds potential as a functional food for obesity prevention and treatment.