In experiments in mice, the researchers found that TOFA is effective at improving insulin sensitivity and glucose control, lowering triglycerides and improving features of fatty liver disease. When obese mice took the compound, they lost weight from fat but experienced no significant loss of lean muscle mass.<\/p>\n
\u201cBody weight responds to two levers: taking in fewer calories, or spending more energy,\u201d said Anders N\u00e4\u00e4r, a professor of metabolic biology and nutrition at UC Berkeley and senior author of the study. \u201cGLP-1s work almost entirely on the first, so we went after the second.\u201d<\/p>\n
TOFA was first discovered in the 1970s and is known for being part of a class of compounds called ACC inhibitors, which help block the production of lipids in the body. Though several ACC inhibitors reached mid-stage clinical testing, none has been approved for metabolic disease. This is largely because many of these compounds can also raise triglycerides, posing a significant risk to heart health.\u00a0<\/p>\n
![\"Three](\"https:\/\/www.newsbeep.com\/us-ca\/wp-content\/uploads\/2026\/08\/20260820_Naar-Lab-5830_BN-1024x585.jpg\")
Graduate student Rachelle Stark (left), Professor Anders N\u00e4\u00e4r and postdoctoral fellow Chu Zhu in the Anders N\u00e4\u00e4r lab at Berkeley. <\/p>\n
Mathew Burciaga\/UC Berkeley<\/p>\n
In the new study, the researchers found that TOFA doesn\u2019t just act as an ACC inhibitor, but also activates PPAR\u03b1 and PPAR\u03b4, cellular receptors which turn on genes that let cells take up fat and burn it for energy. In mice, this caused the cells to burn up to 18% more energy with no change in physical activity or increase in body temperature. Perhaps because of this dual mechanism, TOFA also did not raise triglycerides like other ACC inhibitors.\u00a0<\/p>\n
\u201cTOFA appears to engage a coordinated metabolic response,\u201d said study first author Justin Y. Lee, a postdoctoral student at UCSF who conducted the research as a Ph.D. student at Berkeley. \u201cIt is not simply blocking lipid synthesis. It is also activating energy expenditure pathways that may help the body handle excess lipid and glucose more effectively.\u201d<\/p>\n
When the researchers tried giving mice two separate compounds \u2014 one to block lipid production and a second to boost energy expenditure \u2014 they found that the combination was not as effective at improving overall metabolic health as TOFA alone.\u00a0<\/p>\n
The researchers also explored whether TOFA could be used together with GLP-1 medications like semaglutide, which is sold under the brand names Ozempic or Wegovy, and tirzepatide, which is sold as Mounjaro and Zepbound. In mice, they found that combining TOFA with these GLP-1 drugs led to greater improvements in body weight, glucose control, insulin levels and triglycerides than either treatment alone.\u00a0<\/p>\n
\u201cIn our combination experiments, TOFA worked additively or synergistically with the GLP-1 appetite suppressing drugs, so we view it as complementary rather than as a replacement,\u201d N\u00e4\u00e4r said.\u00a0<\/p>\n
The researchers caution that TOFA has only been studied in animals, and its safety and efficacy in humans has yet to be tested. With support from Berkeley\u2019s life sciences entrepreneurship ecosystem, including Nucleate and Berkeley SkyDeck<\/a>, they have founded a new company ReRx Therapeutics<\/a> to help carry this work to patients.\u00a0<\/p>\n The work was supported by discretionary funds from UC Berkeley, with assistance from the UCSF Liver Center and the University of Michigan Animal Phenotyping Core. Additional authors include Chi Zhu, Melissa A. Boldridge, Rachelle L. Stark, Lei Xu, Federico Gonzalez, Xin Tang, Kaitlyn T. Dang and Kook Son of Berkeley; Gracia Bonilla, Kashish Chetal and Ruslan I. Sadreyev of Massachusetts General Hospital; Kosuke Watari and Michael Karin of the University of California, San Diego; Christina Papa and Bilal N. Sheikh of the Helmholtz Center Munich; Prabha Ibrahim of ReRx Therapeutics.<\/p>\n Conflict of interest statement: Anders N\u00e4\u00e4r, Justin Lee and Prabha Ibrahim are co-founders or officers and equity holders of ReRx Therapeutics, which has optioned UC Berkeley intellectual property related to this work.<\/p>\n","protected":false},"excerpt":{"rendered":"Over the past five years, medications called GLP-1s have revolutionized the treatment of metabolic disorders like obesity, diabetes…\n","protected":false},"author":2,"featured_media":439858,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[1570,143,145,144,8939],"class_list":["post-439857","post","type-post","status-publish","format-standard","has-post-thumbnail","category-oakland","tag-health","tag-oakland","tag-oakland-headlines","tag-oakland-news","tag-press-releases"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/posts\/439857","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/comments?post=439857"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/posts\/439857\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/media\/439858"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/media?parent=439857"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/categories?post=439857"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us-ca\/wp-json\/wp\/v2\/tags?post=439857"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}