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Project 2: Adipocytes and Metabolic Resiliency Return to Projects

Many botanicals (i.e. raspberry, green tea) are widely marketed and promoted to combat obesity. Unfortunately, the claims made regarding these extracts and other botanicals are not supported by mechanistic studies or clinical trials. In contrast, our studies during the last funding cycle have provided considerable evidence demonstrating the potential of specific botanicals to modulate favorable metabolic effects on adipocyte development and function thus supporting our Center concept of “botano-metabolic resiliency”.

Adipocytes are specialized cells that play a major role in energy homeostasis in vertebrates. A major change that occurs in an individual when progressing to metabolic dysfunction is the inability to resist a gain in fat mass or to maintain adipocyte function when exposed to an obesogenic environment. Adipocyte dysfunction can be caused by an inability to store free fatty acids and by alterations in secreted hormones like & fenugreek [Trigonella foenum graecum L.] whose actions on adipocytes lead to a common metabolic outcome. Specifically, each of these highly distinct botanicals increases adiponectin expression and secretion from adipocytes and there is evidence they can attenuate proinflammatory states. While each likely mediates its effects via different mechanisms and cellular pathways, the common result has important implications for pursuing the fundamental pathways and signals by which botanicals can increase adiponectin expression to mediate botano-metabolic resiliency.

Aim 1: To assess botanical gene interactions in adipose tissue induced by Artemisia scoparia (SCOPA), and its components, and their role in maintaining metabolic health. We have increased our understanding of the effects of SCOPA in the last funding cycle, but there are many unanswered questions. Our preliminary data indicates we have identified several active components in SCOPA that regulate adipocyte development. Our recently published studies demonstrate that SCOPA specifically activates PPARg, a transcription factor that plays a role in adipocyte development and function. SCOPA does not reduce weight gain in high-fat fed mice, yet it does protect against metabolic dysfunction. Thus, it is reasonable to propose – in synergy with the central theme of our Center -- that SCOPA promotes metabolic resiliency. Hence, our goal for the next funding period is to test this hypothesis with respect to SCOPA and its active components. 


Aim 2: To assess the ability of fenugreek supplementation to promote adipose tissue maintenance and induce a microbiota profile that is consistent with metabolic health. Fenugreek is widely used and many studies suggest it has anti-diabetic activity. Our preliminary data indicates that fenugreek can modulate adiponectin expression and secretion in adipocytes. We propose to perform mechanistic studies on fenugreek in relation to adipocyte development and function in order to elucidate the mechanisms by which it may promote metabolic health. We will also perform studies to determine how fenugreek modulates gut microbiota. Mice fed a high fat diet will be used to test our hypothesis that fenugreek promotes health and has anti-diabetic activity. This aim is based on a large body of literature that supports health maintenance effects of fenugreek We will examine the effects of fenugreek and its components on adipose tissue function and we will assess its ability to alter gut microbiota. We predict that dietary supplementation with fenugreek will be accompanied by a microbiota profile that is consistent with metabolic health.

Project 2: Recent publications

Knott EJ, Richard AJ, Ribnicky DM, Mynatt RM, Stephens JM and Bruce-Keller A. Fenugreek supplementation during high fat feeding improves specific markers of metabolic health. Scientific Reports 2017;6;7(1):12770.


Obanda D, Zhao P, Richard AJ, Ribnicky D, Cefalu WT, Stephens JM. (2016) Stinging nettle (Urtica dioica L.) attenuates FFA induced ceramide accumulation in 3T3-L1 adipocytes in an adiponectin dependent manner. PLOS One 2016;11:e0150252. PMCID: PMC4777364


Fuller S, Stephens JM. Diosgenin, 4-Hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome. Advances in Nutrition 2015;6:189-197. PMCID: PMC4352177


Richard AJ, Fuller S, Fedorcenco V, Beyl R, Burris TP, Mynatt RL, Ribnicky DM, Stephens JM. Artemisia scoparia enhances adipocyte development and endocrine function in vitro and enhances insulin action in vivo. PLOS One 2014;9(6):e98897. PMCID: PMC4051605


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