The quest for effective weight loss strategies is ongoing, with researchers constantly exploring novel approaches. Emerging research suggests a potential link between white light exposure and weight management. This article delves into the science behind this connection, examining studies that investigate the impact of light, particularly blue light and bright white light, on fat cells, metabolism, and appetite.
The Influence of Sunlight on White Fat Cells
A study by researchers at the University of Alberta, led by Peter Light, investigated the impact of sunlight on subcutaneous white adipose tissue (scWAT) cells, found just beneath our skin. These cells are the major fat depot in humans and a central player in regulating whole-body metabolism. White fat stores calories, and when dysfunctional, it can contribute to cardiometabolic disorders like obesity, diabetes, and heart disease.
The researchers discovered that scWAT cells tend to shrink when exposed to the sun’s blue light. When blue light wavelengths penetrate the skin and reach the fat cells, lipid droplets reduce in size and are released out of the cell.
Low-Level Laser Therapy (LLLT) and Fat Reduction
Low-level laser therapy (LLLT) is used in medical applications. A study evaluated the effect of a 635-680 nm, 10-mW diode laser radiation on treated fat cells. Fat cells were treated in vivo with 1.2-3.6 J/cm2 of energy from the laser for 2 to 6 min. Eighty percent of the fat was released from the fat cells after 4 min of laser light exposure and 99% was released after 6 min of exposure. After exposure to the laser light, pores in fat cells were visible by scanning electron microscope.
A blinded clinical trial was conducted to describe the application of low-level laser therapy to local fat reduction for cosmetic purposes. Forty healthy men and women between the ages of 18-65 years, inclusive, and body mass index (BMI) no greater than 29.9 kg/m2 were randomized in a 1:1 ratio to an experimental laser treatment or to a control laser treatment. Subjects could not be using light sensitizing agents, diuretics, or undergoing photodynamic therapy. Subjects were required to have a stable weight, gaining or losing no more than 2.5 kg in 6 months prior to the trial. Subjects could not be on a weight reduction regimen, and they were asked not to change their diet or exercise habits during the trial.
Read also: Jamie White's resilience shines in her weight loss story
Each subject had two treatments per week for a total of eight treatments over 4 weeks. Each treatment session lasted approximately 30 min. The two multiprobes were placed over the waist bilaterally in three positions as well as two enhancement probes that were placed to both sides of the inguinal region and the laser was activated for 10 min in each of these positions to encompass the waist from the back to the front.
Each treatment gave a 0.4-0.5 cm loss in waist girth. Cumulative girth loss after 4 weeks was −2.15 cm (−0.78 ± 2.82 vs. 1.35 ± 2.64 cm for the control group, p < 0.05). A blinded evaluation of standardized pictures showed statistically significant cosmetic improvement after 4 weeks of laser treatment. LLLT achieved safe and significant girth loss sustained over repeated treatments and cumulative over 4 weeks of eight treatments.
The fat cells that came into contact with plasma or plasma with white blood cells were lysed in both the laser treated and the control plate, but cells in the control wells or in wells with heat-inactivated plasma were not lysed. The laser-irradiated wells containing serum had significantly greater increases in triglycerides than the non-irradiated wells containing serum. The laser-irradiated wells containing heat-inactivated serum had a significantly greater increase in triglycerides than the non-irradiated wells containing heat-inactivated serum. The laser-irradiated wells with serum had significantly lower glycerol levels than the non-irradiated group.
Cysteine Deficiency and Rapid Weight Loss
Research has shown that cysteine deficiency induces the most weight loss compared with all other essential amino acids, resulting in a 30% reduction of body weight within 7 days. Experiments have elucidated a coordinated mechanism characterized by the rapid induction of ISR and OSR, accompanied by increased GDF15 and FGF21, and a reduction in CoA levels resulting in metabolic inefficiency.
Cysteine deprivation in Cse−/− mice, but not in heterozygous and wild-type (WT) mice, led to the largest weight loss compared with other EAAs. A cysteine-free (no-Cys) diet induced weight loss exclusively in Cse−/− mice, indicating that depletion of newly absorbed and synthesized cysteine is necessary for the effect. Weight loss was completely prevented by supplying cysteine through either N-acetylcysteine (NAC) or GSH.
Read also: Are egg white chips keto-friendly?
Cse−/− mice on the no-Cys diet exhibited a 30% reduction in daily food intake, from 3.5 g to 2.4 g per day, while no difference was observed in Cse+/− mice on the control or no-Cys diets (3.4 g in both). While CR of 2.1 g per day led to a weight loss of only 15-16% in the control mice, the Cse−/− mice on the no-Cys diet experienced a substantial 31.5% weight loss within 1 week. At least 15% of the weight loss in Cse−/− mice could not be explained by reduced food intake alone. By contrast, for isoleucine and valine, the amount of weight loss unexplained by reduced food intake was 8% and 6%, respectively, as reported previously. For other EAAs, such as tryptophan and phenylalanine, the entire weight loss was accounted for by reduced food intake.
WT mice on a CR diet (2.1 g per day) devoid of methionine and cysteine lost approximately 30% of their body weight within 1 week as compared to those on a diet devoid of methionine and tryptophan that lost only 20%. This strongly suggests that the benefits of SAAR are primarily driven by cysteine limitation.
After mice on the no-Cys diet were reverted to a standard chow diet, they regained approximately two-thirds of the lost weight within 2 days and fully recovered within 4 days. When returned to the no-Cys diet, the mice promptly resumed losing weight at a similar rate, which was once again reversed immediately after reintroduction to the standard chow. This pattern highlights the high reversibility of cysteine-deprivation-induced weight loss without apparent detrimental effect.
Metabolic Changes and Fat Loss Due to Cysteine Deficiency
Cse−/− mice on a no-Cys diet, the respiratory exchange ratio (RER) progressively decreased from day 1 to day 3, suggesting increased usage of fat as fuel. DEXA scans revealed a substantial reduction in fat content in Cse−/− mice on day 7 of the no-Cys diet. No differences were observed between Cse−/− and Cse+/− mice when provided with the control diet.
Histological studies of white adipose tissue revealed that Cse−/− mice deprived of cysteine exhibited higher fat loss from individual adipocytes by day 3 and, by day 7, there was near complete depletion of fat content throughout the tissue. Caspase-3 staining on day 7 revealed that, despite substantial fat loss, there was no detectable adipocyte cell death.
Read also: The White Foods Diet Plan
By day 3 in Cse−/− mice on a no-Cys diet, a notable proportion of adipocytes that contained multiple small fat droplets instead of a single large droplet, resembling brown/beige adipose tissue. Immunostaining of the fat pad for UCP1 revealed robust browning of white adipose tissue, which on day 3 was faster and more pronounced than previously reported after 4 weeks of CR. Moreover, there was a rapid loss of visceral fat in Cse−/− mice on a no-Cys diet.
Transcriptional Responses to Cysteine Depletion
Gene Ontology (GO) enrichment analysis of genes upregulated in the liver of Cse−/− mice on a no-Cys diet revealed prominent categories such as ‘cellular response to xenobiotic stimulus’, ‘GSH’ and ‘small molecule’ metabolic processes. The latter category revealed strong upregulation of genes associated with ISR, including amino acid synthesis and one-carbon metabolism (Mthfd2, Pycr1, Asns, Psat1), tRNA charging, amino acid transporters (Slc7a1, Slc1a4, Slc3a2) and various stress-response genes (Fgf21, Gdf15, Ddit3, Trib3, Atf5, Atf6). Genes in the ‘cellular response to xenobiotic stimulus’ and ‘glutathione metabolic processes’ categories (Nqo1, Gstm1-Gstm4, Gsta1, Gsta2, Srxn1) are characteristic of NRF2-regulated OSR.
Retatrutide: A Triple Agonist for Weight Loss
Retatrutide activates three receptors: GLP-1, GIP, and glucagon. Glucagon makes the liver break down glycogen, [which is] stored sugar,” Dr. Ghosh explains. “That has the potential to not only increase how much energy you're putting out from your body, but [it] also deplete some of those stores.” It may help you burn more calories both from the activity you do, and simply while at rest. Reta could help mitigate that physiologic change, she says, but emphasizes that more research is needed to confirm this.
A phase 2 clinical trial published in The New England Journal of Medicine in 2023, found that people with obesity who took a 12-milligram dose for 48 weeks saw a mean weight reduction of 24.2 percent. Research has also shown that the average weight loss of someone on semaglutide is about 15 percent, Dr. Mehal says; people on tirzepatide come in at an average around 20 percent.
Retatrutide is also being studied for its potential to reduce the risk of other conditions associated with obesity, such as liver disease and cardiovascular disease, Dr. Ghosh says, adding that the data so far is promising and could make it more likely that insurance companies will cover the drug.
The Melanopsin/TRPC Pathway in scWAT Adipocytes
Human scWAT possesses a blue light-sensitive current that is mediated through a melanopsin/TRPC signaling pathway. The amplitudes of the light-sensitive currents are very small and may be readily inactivated under the broad spectrum white light conditions commonly used in electrophysiology.
The unitary single channel conductance of TRPC1 and 3 is between 17-60 pS. Assuming that a single TRPC channel is open 50% of the time when activated and generates a current of ~1-3 pA, a typical blue light-sensitive current of 50 pA indicates the presence of only ~30-100 TRPC channels being activated at the adipocyte cell surface.
The Impact of Daily Blue Light Exposure on Adipocytes
3T3-L1 differentiated adipocytes exposed to blue (460 nm) light at an intensity of 2.9 mW/cm2 that generates stable currents for 4 hours daily over 13 consecutive days. Visual inspection of cells stained for lipid with Oil Red-O suggested reduced lipid content in the light-treated group compared to the control (dark) group. A significant increase in glycerol release at day 11 and day 14 was observed in the light treated group when compared to the control (dark) group. Adipocytes in the light treated group contained significantly fewer lipid droplets compared to the control (dark) group that were also significantly smaller in size. Blue light-exposed adipocytes secreted significantly less leptin at days 11 and 14 when compared to the control (dark) group. Adipocytes exposed to blue light also secreted lower amounts of adiponectin, with significant changes apparent starting at exposure day 5.
Bright Light Therapy for Weight Management
A crossover, placebo-controlled, randomized clinical trial was performed between November and April in Novosibirsk, Russia (55° N). The trial comprised a 3-week in-home session of morning bright light treatment using a device of light-emitting diodes and a 3-week placebo session by means of a deactivated ion generator, separated by an off-protocol period of at least 23 days. With light, compared to the placebo session, weight did not reduce significantly, but percentage fat, fat mass, and appetite were significantly lower (average fat reduction 0.35 kg). The latter two results remained significant after excluding seasonal-dependent subjects from the analysis. Irrespective of the type of intervention, seasonal-dependent subjects had greater weight and fat mass changes during treatment (decline p ℋ 0.036) or between sessions (regain p ℋ 0.003).
The light-emitting diodes (LEDs) of the SAD Light produced white light with enhanced blue wavelengths (peak at 461 nm) with an intensity of 1,300 lux at a distance of 41 cm. The blue light is important to exert biological effects.
Over the 3 weeks of light session, weight (p ℋ 0.0001 by rANOVA), fat mass (p = 0.0009 by rANOVA), and appetite (p = 0.0004 by Friedman test) decreased and energy levels (p ℋ 0.0001 by Friedman test) increased. Percentage body fat scarcely reduced (p = 0.13, one-way rANOVA) and mood levels scarcely augmented (p = 0.057, Friedman test). Following the 3 weeks of placebo session, only weight and energy levels changed; the changes were in the same direction as during the light session, but with lower probability levels (p = 0.0049 and p = 0.020, respectively); the other main outcome measures did not change (p > 0.48). Whereas weight loss was not greater during light sessions (p = 0.11, effect size d = 0.40), the fat mass reduced pronouncedly, resulting in a significantly lower percentage body fat after the 2nd week of light treatment already. Appetite markedly diminished to the end of light versus placebo sessions, mood somewhat improved. Energy levels were not significantly higher at the end of light versus placebo session.
Irrespective of the type of intervention, ‘seasonals’ (n = 10), compared to ‘non-seasonals’ (n = 24), lost more weight and fat mass (group Ч time interaction, p ℋ 0.036). Additionally, seasonals regained weight and fat mass more easily between the sessions (p ℋ 0.003 compared to non-seasonals), even to a greater level than pre-study.