Building on previous findings that showed that NCT and NFT are potent activators of HNF4α, a central metabolic regulator that is impaired by elevated levels of fat in the bloodstream resulting from chronic overeating, the new study found that mice fed a high fat diet and also consuming doses of NCT gained less weight on a high-fat diet compared to non-supplemented lab animals also consuming a high fat diet.
The study, published in Cell Death & Disease, a Nature journal, is a continuation of the announcement last year that NCT and NFT have a remarkable ability to clear fat from the livers of mice in preclinical research.
The earlier work had identified NCT and NFT in black pepper, but Brightseed’s Forager platform has now found both compounds in hemp hulls.
“Forager enables us to quickly traverse the molecular world of plants and find extraordinary prospects for new health solutions, often in places that are least expected,” said Sofia Elizondo, Co-founder and COO of Brightseed.
“Hemp is one of the most sustainable and versatile crops on the planet, and hemp seeds, or the hearts, are celebrated for their dense nutritional profile. The irony is that we’ve been tossing the wrapper of hemp hearts without realizing they are a potential goldmine for health. Armed with new insight, we can make better use of this sustainable resource.”
Speaking to NutraIngredients-USA in 2020, Brightseed CEO Jim Flatt explained that the Forager platform is designed to, “gain a much deeper understanding of the compounds, what’s called the dark matter of nutrition: these 99% of compounds that have yet to be characterized. With that, we’re able to create a much broader library of compounds from which to make discoveries.
“We have a digital model of human health to make predictions, and this is where a lot of the artificial intelligence comes in to be able to make increasingly accurate predictions about the functions and benefits of these small molecules, these phytonutrients,” he added.
The first preclinical study on NCT and NFT published last year (Cell Death & Disease, 12, 603) showed how these plant bioactives triggered a total body reset in mice fed a high-fat diet. When given certain doses of NCT and NFT, scientists observed other significant health benefits in mice, including reduced liver fat, regulated lipid levels, restored organ function, as well as increased insulin levels in human cells, signaling a resetting and restoring of metabolism from poor to healthy.
The new study showed the compounds reduced body weight gain and accumulation of liver fat together with a reduction in liver inflammation when mice were placed on a long-term high fat diet.
Moreover, NCT and NFT activated fat processing through a novel mechanism not previously reported in published literature.
“Thus, there appear to be at least two independent effects of HNF4α agonism on fat storage: an immediate effect on through lipophagy and a longer-term effect on mitochondrial mass leading to increased mitochondrial function, including fatty acid oxidation,” wrote scientists in Cell Death & Disease.
Clinical trials are needed to confirm the potential impact of NCT and NFT in humans, and such trials are ongoing, a spokesperson for Brightseed told us.
The liver is the body’s primary metabolic organ, and a healthy liver helps avoid metabolic conditions such as type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD).
NAFLD is the most prevalent liver abnormality in Western countries and parallels the epidemic of metabolic syndrome, obesity and diabetes. Frequently disabling and occasionally leading to cirrhosis, fatty liver disease currently costs the US health care system about $32 billion annually.
Source: Cell Death & Disease
2022, Volume 13, 89 doi: 10.1038/s41419-022-04521-5
“Long-term oral administration of an HNF4α agonist prevents weight gain and hepatic steatosis by promoting increased mitochondrial mass and function”
Authors: V. Veeriah, et al.